SPECC1L Gene

Name	sperm antigen with calponin homology and coiled-coil domains 1-like
Description	This gene encodes a coiled-coil domain containing protein. The encoded protein may play a critical role in actin-cytoskeletal reorganization during facial morphogenesis. Mutations in this gene are a cause of oblique facial clefting-1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. A read-through transcript composed of SPECC1L (sperm antigen with calponin homology and coiled-coil domains 1-like) and the downstream ADORA2A (adenosine A2a receptor) gene sequence has been identified, but it is thought to be non-coding. [provided by RefSeq, Jun 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSPECC1L is a multifunctional cytoskeletal protein essential for proper embryonic development. Its loss‐of‐function disrupts normal craniofacial morphogenesis, leading to severe midline defects such as oblique facial clefts, cleft lip and palate, hypertelorism, and other features observed in syndromes like Teebi hypertelorism and autosomal dominant forms of Opitz G/BBB. Animal models, including murine, zebrafish, and Drosophila systems, have demonstrated that SPECC1L deficiency compromises facial primordial proliferation, fusion, and neural crest cell delamination, establishing its critical role in tissue movement and fusion during development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, SPECC1L colocalizes with microtubules and filamentous actin, and it plays a pivotal role in organizing the actin cytoskeleton and regulating adherens junction dynamics. Its activity is closely linked with cell adhesion and migration, as evidenced by studies showing that disruption of SPECC1L function leads to abnormal actin‐cortical reorganization, altered expression and distribution of junction proteins, and impaired PI3K–AKT signaling. Moreover, direct interactions with components such as MYPT1 help balance the distribution of myosin phosphatase complexes between microtubule and actin networks, further underscoring its importance in cytoskeletal regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in SPECC1L have been implicated in a spectrum of developmental syndromes. Beyond craniofacial anomalies, aberrant SPECC1L function has been associated with congenital diaphragmatic hernia, branchial fistulae, and other ventral midline defects. These genotype–phenotype correlations highlight the dosage sensitivity of SPECC1L, with distinct missense and truncation mutations producing variable effects on tissue fusion and morphogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its developmental roles, SPECC1L participates in oncogenic processes when involved in fusion events. Fusions between SPECC1L and receptor tyrosine kinases such as NTRK, as well as with transcriptional regulators like BCL6, have been identified in pediatric central nervous system tumors, extracranial solid tumors, and nasopharyngeal carcinomas. These rearrangements result in mislocalization and altered function of the fusion partner domains, promoting cytokine‐independent growth and oncogenic transformation that are sensitive to targeted inhibitor therapies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, broader transcriptomic analyses have uncovered SPECC1L as a node in complex chimeric RNA networks and as a contributor to disease‐associated regulatory circuits. Elevated SPECC1L levels have been linked with increased risk in conditions such as late onset Alzheimer’s disease, suggesting that its expression may have wider implications beyond structural developmental defects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Irfan Saadi, Fowzan S Alkuraya, Stephen S Gisselbrecht, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deficiency of the cytoskeletal protein SPECC1L leads to oblique facial clefting."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2011.05.023"}], "href": "https://doi.org/10.1016/j.ajhg.2011.05.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21703590"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21703590"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lisa Gfrerer, Valeriy Shubinets, Tatiana Hoyos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional analysis of SPECC1L in craniofacial development and oblique facial cleft pathogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Plast Reconstr Surg (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PRS.0000000000000517"}], "href": "https://doi.org/10.1097/PRS.0000000000000517"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25357034"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25357034"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Elizabeth J Bhoj, Dong Li, Margaret H Harr, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expanding the SPECC1L mutation phenotypic spectrum to include Teebi hypertelorism syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.37217"}], "href": "https://doi.org/10.1002/ajmg.a.37217"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26111080"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26111080"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Nathan R Wilson, Adam J Olm-Shipman, Diana S Acevedo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPECC1L deficiency results in increased adherens junction stability and reduced cranial neural crest cell delamination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep17735"}], "href": "https://doi.org/10.1038/srep17735"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26787558"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26787558"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Chiara Migliore, Anna Vendramin, Shane McKee, et al. "}, {"type": "b", "children": [{"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SPECC1L"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Mutations Are Not Common in Sporadic Cases of Opitz G/BBB Syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes (Basel) (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/genes13020252"}], "href": "https://doi.org/10.3390/genes13020252"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35205294"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35205294"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Irfan Saadi, Jeremy P Goering, Brittany M Hufft-Martinez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPECC1L: a cytoskeletal protein that regulates embryonic tissue dynamics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Soc Trans (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BST20220461"}], "href": "https://doi.org/10.1042/BST20220461"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37345651"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37345651"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Everett G Hall, Luke W Wenger, Nathan R Wilson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPECC1L regulates palate development downstream of IRF6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddaa002"}], "href": "https://doi.org/10.1093/hmg/ddaa002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31943082"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31943082"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Virja Mehta, Nathalie Decan, Sarah Ooi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPECC1L binds the myosin phosphatase complex MYPT1/PP1β and can regulate its distribution between microtubules and filamentous actin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2023.102893"}], "href": "https://doi.org/10.1016/j.jbc.2023.102893"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36634848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36634848"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "K Taylor Wild, Tia Gordon, Elizabeth J Bhoj, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Congenital diaphragmatic hernia as a prominent feature of a SPECC1L-related syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.61878"}], "href": "https://doi.org/10.1002/ajmg.a.61878"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32954677"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32954677"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Dong-Anh Khuong-Quang, Lauren M Brown, Marie Wong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recurrent "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SPECC1L-NTRK"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " fusions in pediatric sarcoma and brain tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cold Spring Harb Mol Case Stud (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/mcs.a005710"}], "href": "https://doi.org/10.1101/mcs.a005710"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33144287"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33144287"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Shuo-Gui Fang, Tian-Liang Xia, Jian-Chang Fu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BCL6-SPECC1L: A Novel Fusion Gene in Nasopharyngeal Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Technol Cancer Res Treat (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/15330338221139981"}], "href": "https://doi.org/10.1177/15330338221139981"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36412101"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36412101"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Sarah Djebali, Julien Lagarde, Philipp Kapranov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence for transcript networks composed of chimeric RNAs in human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0028213"}], "href": "https://doi.org/10.1371/journal.pone.0028213"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22238572"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22238572"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Sergio Branciamore, Grigoriy Gogoshin, Andrei S Rodin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Changes in expression of VGF, SPECC1L, HLA-DRA and RANBP3L act with APOE E4 to alter risk for late onset Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-024-65010-7"}], "href": "https://doi.org/10.1038/s41598-024-65010-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38942763"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38942763"}]}]}]}
Synonyms	CYTSA, OBLFC1
Proteins	CYTSA_HUMAN
NCBI Gene ID	23384
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SPECC1L has 6,057 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 104 datasets.

Click the + buttons to view associations for SPECC1L from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SPECC1L Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SPECC1L gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SPECC1L gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of SPECC1L gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of SPECC1L gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of SPECC1L gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SPECC1L gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SPECC1L gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SPECC1L gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SPECC1L gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of SPECC1L gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SPECC1L gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SPECC1L gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SPECC1L protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SPECC1L gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SPECC1L gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SPECC1L gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SPECC1L gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with SPECC1L gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of SPECC1L gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing SPECC1L protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SPECC1L gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SPECC1L protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SPECC1L protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SPECC1L protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SPECC1L gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SPECC1L gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with SPECC1L gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SPECC1L gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for SPECC1L protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving SPECC1L gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SPECC1L gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SPECC1L gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SPECC1L gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SPECC1L gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SPECC1L gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SPECC1L gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SPECC1L gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing SPECC1L from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SPECC1L gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing SPECC1L from the GeneSigDB Published Gene Signatures dataset.