RIN2

Chr 20AR

Ras and Rab interactor 2

Also known as: MACS, RASSF4

NCBI Gene: 54453 ENSG00000132669 UniProt: Q8WYP3 OMIM: 610222

The protein functions as a guanine nucleotide exchange factor for RAB5, regulating membrane trafficking in the early endocytic pathway. Biallelic mutations cause macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, a connective tissue disorder affecting elastic tissues with autosomal recessive inheritance. The gene shows low constraint to loss-of-function variation (pLI 0.0008, LOEUF 0.549), consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The RAB5 protein is a small GTPase involved in membrane trafficking in the early endocytic pathway. The protein encoded by this gene binds the GTP-bound form of the RAB5 protein preferentially over the GDP-bound form, and functions as a guanine nucleotide exchange factor for RAB5. The encoded protein is found primarily as a tetramer in the cytoplasm and does not bind other members of the RAB family. Mutations in this gene cause macrocephaly alopecia cutis laxa and scoliosis (MACS) syndrome, an elastic tissue disorder, as well as the related connective tissue disorder, RIN2 syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Macrocephaly, alopecia, cutis laxa, and scoliosisMIM #613075

UniProtMACS syndrome

Clinical highlights

Gene-disease validity (ClinGen)

RIN2 syndrome · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.55

LOEUF

LOF

Mechanism· G2P