MVB12B

Chr 9

multivesicular body subunit 12B

Also known as: C9orf28, FAM125B

NCBI Gene: 89853 ENSG00000196814 UniProt: Q9H7P6 OMIM: 621454

The protein is a component of the ESCRT-I complex that sorts ubiquitinated cargo proteins from the plasma membrane into endosomal vesicles and multivesicular bodies. The gene has a relatively low LOEUF score (0.462) suggesting intolerance to loss-of-function variants, but no specific human diseases or inheritance patterns have been established for MVB12B mutations based on the provided information.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a component of the ESCRT-I complex, a heterotetramer, which mediates the sorting of ubiquitinated cargo protein from the plasma membrane to the endosomal vesicle. ESCRT-I complex plays an essential role in HIV budding and endosomal protein sorting. Depletion and overexpression of this and related protein (MVB12A) inhibit HIV-1 infectivity and induce unusual viral assembly defects, indicating a role for MVB12 subunits in regulating ESCRT-mediated virus budding. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.46

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.559

Z-score 3.29

OE 0.20 (0.10–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.67Z-score

OE missense 0.65 (0.56–0.76)

119 obs / 182.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.20 (0.10–0.46)

0≤0.351.4

Missense OE?0.65 (0.56–0.76)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 4 / 19.8Missense obs/exp: 119 / 182.6Syn Z: -0.25

Background carrier burden — how many people carry a rare variant somewhere in MVB12B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

345 rare PASS variants

Rare truncating (LoF)

1 in 2,300

47 rare PASS variants

Rare synonymous (reference)

1 in 180

169 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MVB12B. 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 230	1 in 2,100
South Asian	~43k	1 in 230	1 in 1,200
Remaining (unassigned)	~30k	1 in 160	≈ 1 in 30,000
European (Finnish)	~27k	1 in 480	1 in 2,200
Admixed American	~22k	1 in 160	none seen
African / African American	~21k	1 in 200	1 in 2,200
East Asian	~20k	1 in 190	1 in 2,400
Ashkenazi Jewish	~13k	1 in 870	none seen
Middle Eastern	~2,884	1 in 410	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): 9 of 10 coding exons well covered in gnomAD exomes; exon 1 poorly covered. Genomes: 9 of 10 (exon 1 below).? see exons ↓