TBC1D32

Chr 6AR

TBC1 domain family member 32

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

NCBI Gene: 221322ENSG00000146350UniProt: Q96NH3

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]

Primary Disease Associations & Inheritance

Alsahan-Harris syndromeMIM #621307
AR
Orofaciodigital syndrome IXMIM #258865
AR
Retinitis pigmentosa 100MIM #621280
AR
402
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TBC1D32
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
402 total variants — no pathogenic classifications of 402 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.90LOEUF
pLI 0.000
Z-score 2.23
OE 0.72 (0.57–0.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.04Z-score
OE missense 1.00 (0.93–1.06)
622 obs / 624.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.72 (0.57–0.90)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.93–1.06)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.11
0≤1.21.6
LoF obs/exp: 52 / 72.5Missense obs/exp: 622 / 624.6Syn Z: -1.26

ClinVar Variant Classifications

402 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

TBC1D32 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TBC1D32-related ciliopathy

moderate
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersEye
G2P ↗
splice region variantframeshift variantmissense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Alsahan-Harris syndrome

MIM #621307

Molecular basis of disorder known

Autosomal recessive

Orofaciodigital syndrome IX

MIM #258865

Molecular basis of disorder known

Autosomal recessive

Retinitis pigmentosa 100

MIM #621280

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TBC1D32 variants disrupt retinal ciliogenesis and cause retinitis pigmentosa.
Bocquet B et al.·JCI Insight
2023
Diagnosis of TBC1D32-associated conditions: Expanding the phenotypic spectrum of a complex ciliopathy.
Harris SC et al.·Am J Med Genet A
2023Review
Expanding the clinical and molecular spectrum of TBC1D32-related ciliopathy: case reports and literature Review.
Eiumtrakul W et al.·J Hum Genet
2025Review
Genetic variants affecting mitochondrial function provide further insights for kidney disease.
Cañadas-Garre M et al.·BMC Genomics
2024
Exome analyses unravel the genetic architecture of Mendelian dominant nonsyndromic orofacial clefts.
Zuo Y et al.·Genomics
2025
Two novel mutations in TBC1D32 add complexity to the oro-facial-digital syndrome.
García-Bohórquez B et al.·Hum Genomics
2025Case report
Loss-of-Function Variants in TBC1D32 Underlie Syndromic Hypopituitarism.
Hietamäki J et al.·J Clin Endocrinol Metab
2020Case report
Ciliary genes TBC1D32/C6orf170 and SCLT1 are mutated in patients with OFD type IX.
Adly N et al.·Hum Mutat
2014Case report
Novel Potentially Pathogenic Variants in TBC1D32 Cause Non-syndromic Rod-Cone Degeneration.
Sangermano R et al.·Adv Exp Med Biol
2025Case report
Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy.
Van Driest SL et al.·PLoS One
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools