TBC1D3F

Chr 17

TBC1 domain family member 3F

NCBI Gene: 84218 ENSG00000275954 UniProt: A6NER0 OMIM: 610809

The protein acts as a GTPase activating protein specifically for RAB5, which regulates endocytic trafficking at the plasma membrane. This gene shows very low constraint against loss-of-function variants (pLI = 0.00001, LOEUF = 1.95), and no definitive disease associations have been established in the provided data.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable GTPase activator activity. Predicted to be located in endosome and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.95

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.95LOEUF

pLI 0.000

Z-score -1.22

OE 1.70 (0.82–1.95)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.06Z-score

OE missense 1.03 (0.79–1.35)

37 obs / 36.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.70 (0.82–1.95)

0≤0.351.4

Missense OE?1.03 (0.79–1.35)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 6 / 3.5Missense obs/exp: 37 / 36.0Syn Z: 0.38

Background carrier burden — how many people carry a rare variant somewhere in TBC1D3F?

gnomAD v4 · ~670k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

111 rare PASS variants

Rare truncating (LoF)

1 in 1,400

25 rare PASS variants

Rare synonymous (reference)

1 in 920

27 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TBC1D3F. 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)	~524k	1 in 240	1 in 2,100
South Asian	~37k	1 in 120	1 in 1,200
Remaining (unassigned)	~27k	1 in 280	1 in 1,400
Admixed American	~21k	1 in 180	none seen
African / African American	~20k	1 in 650	1 in 1,100
European (Finnish)	~19k	1 in 2,000	none seen
East Asian	~17k	1 in 390	1 in 800
Ashkenazi Jewish	~12k	1 in 470	1 in 1,200
Middle Eastern	~1,833	≈ 1 in 380	none seen

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): 0 of 14 coding exons well covered in gnomAD exomes; exons 4, 7, 8, 9, 10 and 3 more poorly covered; exons 2, 3, 5, 6, 13, 15 marginal. Genomes: 0 of 14 (exons 2, 3, 4, 5, 6 and 9 more below).? see exons ↓