IGHMBP2

Chr 11AR

immunoglobulin mu DNA binding protein 2

Also known as: CATF1, CMT2S, HCSA, HMN6, HMNR1, SMARD1, SMUBP2, ZFAND7

NCBI Gene: 3508 ENSG00000132740 UniProt: P38935 OMIM: 600502

The protein is a helicase that binds specific DNA sequences in the immunoglobulin mu chain switch region. Mutations cause autosomal recessive spinal muscle atrophy with respiratory distress type 1, Charcot-Marie-Tooth disease axonal type 2S, and distal hereditary motor neuronopathy type 1. The pathogenic mechanism appears to involve dominant-negative effects.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a helicase superfamily member that binds a specific DNA sequence from the immunoglobulin mu chain switch region. Mutations in this gene lead to spinal muscle atrophy with respiratory distress type 1. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.952 OMIM phenotypes

Clinical Summary— IGHMBP2

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Gene-Disease Validity (ClinGen)

hereditary peripheral neuropathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.81

OE 0.71 (0.53–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.18Z-score

OE missense 0.98 (0.91–1.05)

580 obs / 592.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.71 (0.53–0.95)

0≤0.351.4

Missense OE?0.98 (0.91–1.05)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 31 / 43.9Missense obs/exp: 580 / 592.1Syn Z: -1.40

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveIGHMBP2-related spinal muscular atrophy with respiratory distressLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6646th %ile

GOF

0.5465th %ile

LOF

0.3162th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.