TBC1D32

Chr 6

TBC1 domain family member 32

Also known as: ALHSA, BROMI, C6orf170, C6orf171, OFD9, RP100

NCBI Gene: 221322 ENSG00000146350 UniProt: Q96NH3

This protein is required for high-level sonic hedgehog responses in the developing neural tube and controls primary cilium structure by coordinating assembly of the ciliary membrane and axoneme. Mutations cause autosomal recessive ciliopathies including Alsahan-Harris syndrome, orofaciodigital syndrome IX, and retinitis pigmentosa 100. These conditions primarily affect craniofacial development, limb formation, and retinal function due to disrupted ciliary signaling pathways.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a TBC-domain containing protein. Studies of a similar protein in mouse and zebrafish suggest that the encoded protein is involved in sonic hedgehog signaling, and that it interacts with and stabilizes cell cycle-related kinase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.90

Clinical Summary— TBC1D32

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Gene-Disease Validity (ClinGen)

ciliopathy · 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

28 unique Pathogenic / Likely Pathogenic· 213 VUS of 371 total submissions

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GeneReview available — TBC1D32

Authoritative clinical overview · Recommended first read

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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?

0.90LOEUF

pLI 0.000

Z-score 2.23

OE 0.72 (0.57–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.04Z-score

OE missense 1.00 (0.93–1.06)

622 obs / 624.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.57–0.90)

0≤0.351.4

Missense OE?1.00 (0.93–1.06)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 52 / 72.5Missense obs/exp: 622 / 624.6Syn Z: -1.26

ClinVar Variant Classifications

371 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic7

VUS213

Likely Benign66

Benign38

Conflicting3

Pathogenic

Likely Pathogenic

213

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	0	10	0	21
Likely Pathogenic	7	0	0	0	7
VUS	3	202	6	2	213
Likely Benign	0	15	23	28	66
Benign	0	13	15	10	38
Conflicting	—				3
Total	21	230	54	40	348

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap TBC1D32 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →