NOMO2

Chr 16

NODAL modulator 2

Also known as: Nomo, PM5

NCBI Gene: 283820 ENSG00000185164 UniProt: Q5JPE7

The protein functions as a component of the multi-pass translocon complex that mediates insertion of multi-pass membrane proteins into cellular membranes. NOMO2 mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and seizures, typically presenting in infancy or early childhood. The condition follows an autosomal recessive inheritance pattern.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein originally thought to be related to the collagenase gene family. This gene is one of three highly similar genes in a region of duplication located on the p arm of chromosome 16. These three genes encode closely related proteins that may have the same function. The protein encoded by one of these genes has been identified as part of a protein complex that participates in the Nodal signaling pathway during vertebrate development. Mutations in ABCC6, which is located nearby, rather than mutations in this gene are associated with pseudoxanthoma elasticum (PXE). Two transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

LOEUF 1.07

Clinical Summary— NOMO2

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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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ClinVar Variants

108 VUS of 123 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.07LOEUF

pLI 0.000

Z-score 1.34

OE 0.66 (0.42–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.03Z-score

OE missense 0.81 (0.72–0.91)

186 obs / 230.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.42–1.07)

0≤0.351.4

Missense OE?0.81 (0.72–0.91)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 12 / 18.1Missense obs/exp: 186 / 230.1Syn Z: 1.04

ClinVar Variant Classifications

123 submitted variants in ClinVar

ClinVar

Classification Summary

VUS108

Likely Benign5

108

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	108	0	108
Likely Benign	4	1	5
Benign	0	0	0
Total	112	1	113

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap NOMO2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →