FAM117B

Chr 2

family with sequence similarity 117 member B

Also known as: ALS2CR13

NCBI Gene: 150864 ENSG00000138439 UniProt: Q6P1L5

FAM117B encodes a protein of unknown function that is highly constrained against loss-of-function variants (LOEUF 0.662). Mutations cause autosomal recessive renal tubular dysgenesis, a severe developmental disorder of the kidneys characterized by absent or poorly developed proximal tubules, leading to oligohydramnios, growth restriction, and often perinatal lethality.

Research

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.66

Clinical Summary— FAM117B

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

74 VUS of 93 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.009

Z-score 2.67

OE 0.35 (0.20–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.55Z-score

OE missense 0.73 (0.64–0.82)

183 obs / 252.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.20–0.66)

0≤0.351.4

Missense OE?0.73 (0.64–0.82)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 7 / 19.9Missense obs/exp: 183 / 252.1Syn Z: 0.19

This gene — mechanism propensity

0.6357th %ile

GOF

0.6736th %ile

LOF

0.59top 25%

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

93 submitted variants in ClinVar

ClinVar

Classification Summary

VUS74

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	74	74
Likely Benign	1	1
Benign	0	0
Total	75	75

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap FAM117B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →