EGFL6

Chr X

EGF like domain multiple 6

Also known as: MAEG, W80

NCBI Gene: 25975 ENSG00000198759 UniProt: Q8IUX8

The protein is a secreted member of the epidermal growth factor repeat superfamily that binds integrin alpha-8/beta-1 and promotes matrix assembly during hair follicle morphogenesis. This gene is extremely intolerant to loss-of-function variation (pLI ~1.0), but no Mendelian diseases have been definitively associated with EGFL6 mutations in humans. Current evidence suggests this gene may be essential for normal development, but additional research is needed to establish clear genotype-phenotype correlations.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the epidermal growth factor (EGF) repeat superfamily. Members of this superfamily are characterized by the presence of EGF-like repeats and are often involved in the regulation of cell cycle, proliferation, and developmental processes. The gene product contains a signal peptide, suggesting that it is secreted; an EGF repeat region consisting of 4 complete EGF-like repeats and 1 partial EGF-like repeat, 3 of which have a calcium-binding consensus sequence; an arg-gly-asp integrin association motif; and a MAM domain, which is believed to have an adhesive function. This gene is expressed early during development, and its expression has been detected in lung and meningioma tumors. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.29

LOEUF

—

Mechanism

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?

1.29LOEUF

pLI 0.000

Z-score 0.51

OE 0.88 (0.62–1.29)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.64Z-score

OE missense 0.88 (0.78–0.99)

189 obs / 215.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.88 (0.62–1.29)

0≤0.351.4

Missense OE?0.88 (0.78–0.99)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 20 / 22.6Missense obs/exp: 189 / 215.3Syn Z: -0.94

Background carrier burden — how many people carry a rare variant somewhere in EGFL6?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

467 rare PASS variants

Rare truncating (LoF)

1 in 2,000

69 rare PASS variants

Rare synonymous (reference)

1 in 280

181 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EGFL6. 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)	~561k	1 in 220	1 in 2,400
South Asian	~36k	1 in 110	1 in 500
Remaining (unassigned)	~31k	1 in 95	1 in 2,400
European (Finnish)	~27k	1 in 630	≈ 1 in 6,700
Admixed American	~23k	1 in 210	1 in 2,900
African / African American	~21k	1 in 120	1 in 2,700
East Asian	~20k	1 in 97	1 in 1,500
Ashkenazi Jewish	~13k	1 in 520	none seen
Middle Eastern	~2,758	1 in 75	≈ 1 in 2,700

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): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓