MARCHF7

Chr 2

membrane associated ring-CH-type finger 7

Also known as: AXO, AXOT, MARCH-VII, MARCH7, RNF177

NCBI Gene: 64844 ENSG00000136536 UniProt: Q9H992 OMIM: 613334

MARCH7 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH proteins add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments (Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Mar 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

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

0.38

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.38LOEUF

pLI 0.662

Z-score 4.31

OE 0.20 (0.12–0.38)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.24Z-score

OE missense 0.97 (0.88–1.05)

348 obs / 360.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.20 (0.12–0.38)

0≤0.351.4

Missense OE?0.97 (0.88–1.05)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 7 / 34.2Missense obs/exp: 348 / 360.6Syn Z: -0.06

Background carrier burden — how many people carry a rare variant somewhere in MARCHF7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 80

896 rare PASS variants

Rare truncating (LoF)

1 in 2,700

75 rare PASS variants

Rare synonymous (reference)

1 in 170

318 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MARCHF7. 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 110	1 in 2,700
South Asian	~43k	1 in 81	1 in 960
Remaining (unassigned)	~30k	1 in 75	≈ 1 in 9,200
European (Finnish)	~27k	1 in 180	≈ 1 in 6,000
Admixed American	~22k	1 in 89	1 in 3,200
African / African American	~21k	1 in 58	1 in 2,200
East Asian	~20k	1 in 60	none seen
Ashkenazi Jewish	~13k	1 in 500	none seen
Middle Eastern	~2,884	1 in 67	none seen

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): 8 of 9 coding exons well covered in gnomAD exomes; exon 9 marginal. Genomes: all 9.? see exons ↓