SDCCAG8

Chr 1

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

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 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 ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.78

Clinical Summary— SDCCAG8

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Gene-Disease Validity (ClinGen)

Bardet-Biedl syndrome 16 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

102 unique Pathogenic / Likely Pathogenic· 400 VUS of 838 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SDCCAG8

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSDCCAG8-related Senior-Loken syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.7035th %ile

GOF

0.6051th %ile

LOF

0.3454th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

838 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45

Likely Pathogenic57

VUS400

Likely Benign255

Benign26

Conflicting30

Pathogenic

Likely Pathogenic

400

VUS

255

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	37	0	8	0	45
Likely Pathogenic	50	2	5	0	57
VUS	9	341	41	9	400
Likely Benign	2	5	122	126	255
Benign	1	0	22	3	26
Conflicting	—				30
Total	99	348	198	138	813

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

96 pathogenic / likely-pathogenic (of 121) ClinVar copy-number / structural variants overlap SDCCAG8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →