RAB5IF

Chr 20AR

RAB5 interacting factor

Also known as: C20orf24, CFSMR2, OPTI, PNAS-11, RCAF1, RIP5

NCBI Gene: 55969ENSG00000101084UniProt: Q9BUV8

Involved in mitochondrial respirasome assembly and multi-pass transmembrane protein insertion into ER membrane. Located in mitochondrion. Part of multi-pass translocon complex. Implicated in craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

?Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2MIM #616994
AR
13
ClinVar variants
10
Pathogenic / LP
0.67
pLI score
0
Active trials
Clinical Summary— RAB5IF
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.67) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 3 VUS of 13 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.60LOEUF
pLI 0.670
Z-score 2.27
OE 0.13 (0.04–0.60)
Moderately constrained

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.
0.51Z-score
OE missense 0.83 (0.67–1.03)
60 obs / 72.2 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.0.13 (0.04–0.60)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.67–1.03)
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.1.41
0≤1.21.6
LoF obs/exp: 1 / 7.9Missense obs/exp: 60 / 72.2Syn Z: -1.72

ClinVar Variant Classifications

13 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic3
VUS3
7
Pathogenic
3
Likely Pathogenic
3
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
3
0
3
VUS
0
2
1
0
3
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0211013

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

View in ClinVar →

Protein Context — Lollipop Plot

RAB5IF · 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

?Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2

MIM #616994

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Defining mitochondrial protein functions through deep multiomic profiling.
Rensvold JW et al.·Nature
2022
Analysis of gut microbiome, host genetics, and plasma metabolites reveals gut microbiome-host interactions in the Japanese population.
Tomofuji Y et al.·Cell Rep
2023
Identification and analysis of mitochondria-related central genes in steroid-induced osteonecrosis of the femoral head, along with drug prediction.
Ma Z et al.·Front Endocrinol (Lausanne)
2024
Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome-1 in two new patients with the same homozygous TMCO1 variant and review of the literature.
Abdelrazek IM et al.·Eur J Med Genet
2023Review
A novel prognostic signature based on four glycolysis-related genes predicts survival and clinical risk of hepatocellular carcinoma.
Chen Z et al.·J Clin Lab Anal
2021
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