FAM50B

Chr 6

family with sequence similarity 50 member B

Also known as: D6S2654E, X5L

NCBI Gene: 26240ENSG00000145945UniProt: Q9Y247

This gene contains an intronless ORF that arose from ancestral retroposition. The encoded protein is related to a plant protein that plays a role in the circadian clock. This gene is adjacent to a differentially methylated region (DMR) and is imprinted and paternally expressed in many tissues. [provided by RefSeq, Nov 2015]

91
ClinVar variants
45
Pathogenic / LP
0.15
pLI score
0
Active trials
Clinical Summary— FAM50B
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
45 Pathogenic / Likely Pathogenic· 42 VUS of 91 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

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.
0.76LOEUF
pLI 0.154
Z-score 2.10
OE 0.29 (0.13–0.76)
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.
2.31Z-score
OE missense 0.59 (0.52–0.68)
149 obs / 252.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.29 (0.13–0.76)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.59 (0.52–0.68)
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.0.80
0≤1.21.6
LoF obs/exp: 3 / 10.3Missense obs/exp: 149 / 252.3Syn Z: 1.69

ClinVar Variant Classifications

91 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic5
VUS42
Likely Benign4
40
Pathogenic
5
Likely Pathogenic
42
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
40
0
40
Likely Pathogenic
0
0
5
0
5
VUS
0
39
3
0
42
Likely Benign
0
3
1
0
4
Benign
0
0
0
0
0
Total04249091

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

View in ClinVar →

Protein Context — Lollipop Plot

FAM50B · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Whole-genome sequencing identifies new candidate genes for nonobstructive azoospermia.
Malcher A et al.·Andrology
2022
Phenotypic spectrum and extent of DNA methylation defects associated with multilocus imprinting disturbances.
Bens S et al.·Epigenomics
2016
Uncovering the phenotypic consequences of multi-locus imprinting disturbances using genome-wide methylation analysis in genomic imprinting disorders.
Kim HY et al.·PLoS One
2023
Stochastic epigenetic mutations as possible explanation for phenotypical discordance among twins with congenital hypothyroidism.
Gentilini D et al.·J Endocrinol Invest
2023
Association between non-Caucasian-specific ASCC1 gene polymorphism and osteoporosis and obesity in Korean postmenopausal women.
Cho HW et al.·J Bone Miner Metab
2020
Array-based DNA methylation analysis in individuals with developmental delay/intellectual disability and normal molecular karyotype.
Kolarova J et al.·Eur J Med Genet
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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