RAB5IF

Chr 20AR

RAB5 interacting factor

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

NCBI Gene: 55969 ENSG00000101084 UniProt: Q9BUV8 OMIM: 619960

The protein is a component of the multi-pass translocon complex that mediates insertion of multi-pass membrane proteins into the ER membrane and acts as an assembly factor for mitochondrial respiratory complexes. Autosomal recessive mutations cause craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.602), and the condition involves craniofacial, skeletal, and neurodevelopmental systems.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2MIM #616994

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.60

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

0.51Z-score

OE missense 0.83 (0.67–1.03)

60 obs / 72.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.13 (0.04–0.60)

0≤0.351.4

Missense OE?0.83 (0.67–1.03)

0≤0.61.4

Synonymous OE?1.41

0≤1.21.6

LoF obs/exp: 1 / 7.9Missense obs/exp: 60 / 72.2Syn Z: -1.72

Background carrier burden — how many people carry a rare variant somewhere in RAB5IF?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 380

238 rare PASS variants

Rare truncating (LoF)

1 in 4,000

52 rare PASS variants

Rare synonymous (reference)

1 in 430

108 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RAB5IF. 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 480	1 in 6,800
South Asian	~43k	1 in 290	1 in 2,100
Remaining (unassigned)	~30k	1 in 350	1 in 5,900
European (Finnish)	~27k	1 in 940	≈ 1 in 8,200
Admixed American	~22k	1 in 190	≈ 1 in 5,600
African / African American	~21k	1 in 300	1 in 930
East Asian	~20k	1 in 290	≈ 1 in 5,000
Ashkenazi Jewish	~13k	≈ 1 in 6,500	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 280	≈ 1 in 2,900

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): 3 of 4 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 4.? see exons ↓