MORN1

Chr 1ARAD

MORN repeat containing 1

NCBI Gene: 79906 ENSG00000116151 UniProt: Q5T089 OMIM: 605267

MORN1 encodes a membrane occupation and recognition nexus protein that localizes to mitochondria and is involved in mitochondrial dynamics and morphology. Mutations cause both dilated cardiomyopathy (type 2E) and hypertrophic cardiomyopathy (type 17) with autosomal recessive and autosomal dominant inheritance patterns. The gene shows extremely low constraint against loss-of-function variants, indicating tolerance to such mutations in the general population.

OMIM ResearchSummary from OMIM

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 2EMIM #619492

Cardiomyopathy, hypertrophic, 17MIM #613873

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Cardiomyopathy, dilated, 2E; Cardiomyopathy, hypertrophic; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.12

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.12LOEUF

pLI 0.000

Z-score 1.10

OE 0.77 (0.54–1.12)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.28Z-score

OE missense 1.05 (0.95–1.15)

308 obs / 294.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.77 (0.54–1.12)

0≤0.351.4

Missense OE?1.05 (0.95–1.15)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 20 / 26.0Missense obs/exp: 308 / 294.2Syn Z: -0.04

Background carrier burden — how many people carry a rare variant somewhere in MORN1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 32

920 rare PASS variants

Rare truncating (LoF)

1 in 320

173 rare PASS variants

Rare synonymous (reference)

1 in 94

269 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MORN1. 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 56	1 in 330
South Asian	~43k	1 in 31	1 in 320
Remaining (unassigned)	~30k	1 in 30	1 in 310
European (Finnish)	~27k	1 in 170	1 in 1,600
Admixed American	~22k	1 in 40	1 in 530
African / African American	~21k	1 in 34	1 in 680
East Asian	~20k	1 in 47	1 in 410
Ashkenazi Jewish	~13k	1 in 120	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 34	1 in 290

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): 12 of 14 coding exons well covered in gnomAD exomes; exons 1, 14 marginal. Genomes: all 14.? see exons ↓