EGFL6

Chr X

EGF like domain multiple 6

Also known as: MAEG, W80

NCBI Gene: 25975 ENSG00000198759 UniProt: Q8IUX8 OMIM: 300239

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

LOEUF 1.29

Clinical Summary— EGFL6

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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

61 VUS of 118 total submissions

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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

ClinVar Variant Classifications

118 submitted variants in ClinVar

ClinVar

Classification Summary

VUS61

Likely Benign6

Benign6

VUS

Likely Benign

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	61	0	61
Likely Benign	3	3	6
Benign	3	3	6
Total	67	6	73

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

View in ClinVar →

76 pathogenic / likely-pathogenic (of 87) ClinVar copy-number / structural variants overlap EGFL6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →