SPECC1L

Chr 22AD

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

Also known as: CYTSA, GBBB2, OBLFC1, TBHS, TBHS1

NCBI Gene: 23384ENSG00000100014UniProt: Q69YQ0OMIM: 614140

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]

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Facial clefting, oblique, 1MIM #600251
AD
Teebi hypertelorism syndrome 1MIM #145420
AD

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
9
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.33
LOEUF· LoF intol.
Multiple*
Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.33LOEUF
pLI 0.859
Z-score 5.49
OE 0.20 (0.13–0.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.60Z-score
OE missense 0.82 (0.76–0.88)
497 obs / 607.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.20 (0.13–0.33)
0≤0.351.4
Missense OE?0.82 (0.76–0.88)
0≤0.61.4
Synonymous OE?1.01
0≤1.21.6
LoF obs/exp: 11 / 54.9Missense obs/exp: 497 / 607.9Syn Z: -0.11

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SPECC1L · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients