AFG2B

Chr 15AR

AAA ATPase AFG2B

Also known as: DFNB119, NEDHLS, SPATA5L1

NCBI Gene: 79029ENSG00000171763UniProt: Q9BVQ7

Enables identical protein binding activity and preribosome binding activity. Involved in ribosomal large subunit biogenesis. Located in cytoplasm and spindle. Implicated in autosomal recessive nonsyndromic deafness. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Deafness, autosomal recessive 119MIM #619615
AR
Neurodevelopmental disorder with hearing loss and spasticityMIM #619616
AR
198
ClinVar variants
33
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— AFG2B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 130 VUS of 198 total submissions

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.
1.07LOEUF
pLI 0.000
Z-score 1.28
OE 0.74 (0.52–1.07)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.86Z-score
OE missense 0.88 (0.80–0.96)
346 obs / 394.1 exp
Tolerant

Mild missense constraint

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.0.74 (0.52–1.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.80–0.96)
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.0.95
0≤1.21.6
LoF obs/exp: 20 / 27.2Missense obs/exp: 346 / 394.1Syn Z: 0.48

ClinVar Variant Classifications

198 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic16
VUS130
Likely Benign14
Benign8
Conflicting3
17
Pathogenic
16
Likely Pathogenic
130
VUS
14
Likely Benign
8
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
12
0
17
Likely Pathogenic
2
13
1
0
16
VUS
0
115
15
0
130
Likely Benign
0
5
0
9
14
Benign
0
4
1
3
8
Conflicting
—3
Total71372912188

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

View in ClinVar →

Protein Context — Lollipop Plot

AFG2B · protein map & ClinVar variants

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

Gene2Phenotype Curations

AFG2B-related sensorineural hearing loss and intellectual disability

moderate
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEar
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Deafness, autosomal recessive 119

MIM #619615

Molecular basis of disorder known

Autosomal recessive

Neurodevelopmental disorder with hearing loss and spasticity

MIM #619616

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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