FAM89B

Chr 11

family with sequence similarity 89 member B

Also known as: LRAP25, MTVR, MTVR1

NCBI Gene: 23625 ENSG00000176973 UniProt: Q8N5H3

FAM89B encodes a protein that negatively regulates TGF-beta signaling by preventing SMAD2 translocation and acts as an adapter mediating recognition of LIMK1 in lamellipodia for actin regulation. The gene has low constraint against loss-of-function variants (pLI 0.05, LOEUF 1.65), and no definitive disease associations have been established in humans. Current evidence is insufficient to determine inheritance patterns or clinical phenotypes associated with FAM89B variants.

ResearchSummary from RefSeq, UniProt

Predicted to enable transcription corepressor binding activity. Predicted to be involved in establishment of cell polarity; negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway; and positive regulation of cell migration. Predicted to be active in cytoplasm and lamellipodium. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.65

LOEUF

Multiple*

Mechanism· predicted

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?

1.65LOEUF

pLI 0.052

Z-score 0.70

OE 0.59 (0.24–1.65)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.05Z-score

OE missense 0.61 (0.46–0.81)

35 obs / 57.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.59 (0.24–1.65)

0≤0.351.4

Missense OE?0.61 (0.46–0.81)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 2 / 3.4Missense obs/exp: 35 / 57.4Syn Z: 0.19

Background carrier burden — how many people carry a rare variant somewhere in FAM89B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

315 rare PASS variants

Rare truncating (LoF)

1 in 6,400

38 rare PASS variants

Rare synonymous (reference)

1 in 810

113 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FAM89B. 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 320	1 in 7,500
South Asian	~43k	1 in 390	1 in 1,600
Remaining (unassigned)	~30k	1 in 190	≈ 1 in 7,600
European (Finnish)	~27k	1 in 320	1 in 4,000
Admixed American	~22k	1 in 260	1 in 3,600
African / African American	~21k	1 in 220	≈ 1 in 5,400
East Asian	~20k	1 in 310	1 in 3,400
Ashkenazi Jewish	~13k	1 in 540	none seen
Middle Eastern	~2,884	1 in 170	≈ 1 in 650

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): 1 of 2 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 2.? see exons ↓