GeneBe

SPECC1L

protein-coding

sperm antigen with calponin homology and coiled-coil domains 1 like

Gene summary

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]

Previous symbols:
  • CYTSA

MANE transcript

NM_015330.6

Inheritance

AD

ClinVar variants

P:16U:259B:131

Top phenotype

Opitz GBBB syndrome, type II

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr22:24,270,817-24,417,739

External References & Databases

Ensembl (ENSG00000100014)NCBI Gene (23384)OMIM (614140)HGNC:29022GenCCUniProt (Q69YQ0)AlphaFoldClinVar (SPECC1L)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~146.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypertelorism, Teebi typeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007780

Submitter: Orphanet

Teebi hypertelorism syndrome 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0800025

Submitter: PanelApp Australia

Teebi hypertelorism syndrome 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0800025

Submitter: G2P

Tessier number 4 facial cleftLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0010850

Submitter: Ambry Genetics

autosomal dominant Opitz G/BBB syndromeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0007779

Submitter: Ambry Genetics

autosomal dominant Opitz G/BBB syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007779

Submitter: Labcorp Genetics (formerly Invitae)

hypertelorism, Teebi typeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0007780

Submitter: Ambry Genetics

commissural facial cleftSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0013300

Submitter: Orphanet

Tessier number 4 facial cleftNO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0010850

Submitter: G2P

hypertelorism, Teebi typeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007780

Submitter: Illumina

Clinical Genomic Database (CGD)

Opitz GBBB syndrome, type IIAD

Manifestation: Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Neurologic

Intervention: Cardiovascular

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 3398011; 17506099; 21703590; 25412741; 26111080Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SPECC1L variants in ClinVar

14 Conditions Cataloged
not providedTotal: 269
Inborn genetic diseasesTotal: 128
SPECC1L-related disorderTotal: 67
not specifiedTotal: 49
Teebi hypertelorism syndrome 1Total: 32
Oculomaxillofacial dysostosisTotal: 15
Teebi hypertelorism syndromeTotal: 15
Autosomal dominant Opitz G/BBB syndromeTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015330.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
62
clinvar
9
clinvar
 72
missense
7
clinvar
8
clinvar
234
clinvar
50
clinvar
10
clinvar
 309
nonsense
1
clinvar
10
clinvar
 11
start loss
0
frameshift
12
clinvar
 12
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total7925911219406

Highest pathogenic variant AF is 0.000025404017

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_015330.6RefSeqNP_056145.515MANE Select
ENST00000314328.14EnsemblENSP00000325785.815MANE Select
NM_001145468.4RefSeqNP_001138940.415Standard
NM_001254732.3RefSeqNP_001241661.314Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
specc1lbDanio rerio

Structure: neural crest cell

Quality: decreased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • cell cycle
  • cell adhesion
  • actin cytoskeleton organization
  • cell division

Cellular Component

  • microtubule organizing center
  • spindle
  • cytosol
  • gap junction
  • actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000314328
Coding exons
15
Length
146923
Individuals with no LoFs
125727
Homozygous LoFs
0
Heterozygous LoFs
21
Defined
125748
p
0.0000835
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.604976080.8180.00003657335
Missense (PolyPhen)138228.910.602862708
Synonymous-0.1062302281.010.00001342159
Loss of Function5.491154.90.2000.00000363624

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000180.00018rare
Latino/Admixed American00.0absent
Ashkenazi Jewish0.0000990.000099rare
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.000110.00011rare
South Asian0.000130.00013rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Involved in cytokinesis and spindle organization. May play a role in actin cytoskeleton organization and microtubule stabilization and hence required for proper cell adhesion and migration. {ECO:0000269|PubMed:21703590}.;
Disease
DISEASE: Facial clefting, oblique, 1 (OBLFC1) [MIM:600251]: A rare form of facial clefting. A facial cleft is any of the fissures between the embryonic prominences that normally unite to form the face. {ECO:0000269|PubMed:21703590}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Opitz GBBB syndrome 2 (GBBB2) [MIM:145410]: A form of Opitz GBBB syndrome, a congenital midline malformation syndrome characterized by hypertelorism, genital-urinary defects such as hypospadias in males and splayed labia in females, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and congenital heart defects. {ECO:0000269|PubMed:25412741}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.108

Intolerance Scores

RVIS EVS
-0.28
RVIS percentile EVS
33.53

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
H
Indispensability pred.
N
Indispensability score
0.114

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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