SDCCAG8

Chr 1AR

SHH signaling and ciliogenesis regulator SDCCAG8

Also known as: BBS16, CCCAP, CCCAP SLSN7, HSPC085, NPHP10, NY-CO-8, SLSN7, hCCCAP

NCBI Gene: 10806 ENSG00000054282 UniProt: Q86SQ7 OMIM: 613524

This gene encodes a centrosome-associated protein that is essential for ciliogenesis and plays a critical role in establishing cell polarity and epithelial lumen formation. Mutations cause autosomal recessive ciliopathies including Bardet-Biedl syndrome 16 and Senior-Loken syndrome 7, which affect multiple organ systems including the retina, kidneys, and other ciliated tissues. The gene is extremely intolerant to loss-of-function variants (pLI ~0), indicating that complete loss of protein function is likely pathogenic.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a centrosome associated protein. This protein may be involved in organizing the centrosome during interphase and mitosis. Mutations in this gene are associated with retinal-renal ciliopathy. [provided by RefSeq, Oct 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Bardet-Biedl syndrome 16MIM #615993

Senior-Loken syndrome 7MIM #613615

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Bardet-Biedl syndrome 16 · AR · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.78

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — SDCCAG8

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.78LOEUF

pLI 0.000

Z-score 2.71

OE 0.56 (0.41–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.10Z-score

OE missense 1.01 (0.93–1.11)

367 obs / 361.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.56 (0.41–0.78)

0≤0.351.4

Missense OE?1.01 (0.93–1.11)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 25 / 44.5Missense obs/exp: 367 / 361.7Syn Z: -0.52

Background carrier burden — how many people carry a rare variant somewhere in SDCCAG8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 60

925 rare PASS variants

Rare truncating (LoF)

1 in 620

178 rare PASS variants

Rare synonymous (reference)

1 in 110

324 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SDCCAG8. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 78	1 in 910
South Asian	~43k	1 in 49	1 in 400
Remaining (unassigned)	~30k	1 in 49	1 in 790
European (Finnish)	~27k	1 in 260	≈ 1 in 6,700
Admixed American	~22k	1 in 53	1 in 790
African / African American	~21k	1 in 46	1 in 520
East Asian	~20k	1 in 65	1 in 470
Ashkenazi Jewish	~13k	1 in 340	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 43	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 16 of 18 coding exons well covered in gnomAD exomes; exons 4, 7 marginal. Genomes: all 18.? see exons ↓