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Consulting OMIM phenotypes...

MEGF9

Chr 9

multiple EGF like domains 9

Also known as: EGFL5

NCBI Gene: 1955 ENSG00000106780 UniProt: Q9H1U4

Predicted to be located in basement membrane and membrane. [provided by Alliance of Genome Resources, Jul 2025]

132

ClinVar variants

22

Pathogenic / LP

0.99

pLI score· haploinsufficient

0

Active trials

Clinical Summary— MEGF9

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

22 Pathogenic / Likely Pathogenic· 102 VUS of 132 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.27LOEUF

pLI 0.988

Z-score 3.69

OE 0.06 (0.02–0.27)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.43Z-score

OE missense 0.75 (0.67–0.84)

197 obs / 262.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.02–0.27)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.67–0.84)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.70

0≤1.21.6

LoF obs/exp: 1 / 17.8Missense obs/exp: 197 / 262.2Syn Z: 2.45

ClinVar Variant Classifications

132 submitted variants in ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic1

VUS102

Likely Benign5

21

Pathogenic

1

Likely Pathogenic

102

VUS

5

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	21	0	21
Likely Pathogenic	0	0	1	0	1
VUS	0	100	2	0	102
Likely Benign	0	5	0	0	5
Benign	0	0	0	0	0
Total	0	105	24	0	129

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

View in ClinVar →

Protein Context — Lollipop Plot

MEGF9 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

MULTIPLE EPIDERMAL GROWTH FACTOR-LIKE DOMAINS 9; MEGF9

MIM #604268 · *

External Resources

Links to major genomics databases and tools

Variant Interpretation

Variant interpretation & classification platform

Franklin by Genoox

AI-powered variant curation and clinical analysis

Genomic literature search for variants and genes

ACMG/AMP variant classification tool

Population Databases

Population allele frequencies & constraint metrics

Genomic variants and phenotypes in rare disease patients

Clinical variant interpretations from submitters worldwide

Short genetic variation database

Gene Resources

Gene annotation, transcripts & comparative genomics

Comprehensive gene information and references

Protein sequence, structure and function

Online Mendelian Inheritance in Man

Human gene compendium

Gene expression across human tissues

Expert Curation

Expert-curated gene-disease validity

Gene Curation Coalition — multi-curator classifications

Rare disease encyclopedia and gene-disease associations

Autism-gene association scoring (SFARI)

Gene panels for rare disease diagnostics (Genomics England)

Leiden Open Variation Database — variant listings

Expert-authored summaries of heritable conditions (NCBI)

Clinical Literature

Landmark / reviewRecent case evidence

Key Publications

Landmark & review papers · by relevance

PubMed

Integrative Transcriptomic Analysis of Peripheral Blood Monocytes in Systemic Sclerosis and Shared Pathogenic Pathways in Autoimmune Diseases.

Chen S et al.·Arch Med Res

2025

A novel smoking cessation behavior based on quit attempts may identify new genes associated with long-term abstinence.

Lori A et al.·Addict Behav

2025

A novel autosomal dominant condition consisting of congenital heart defects and low atrial rhythm maps to chromosome 9q.

van de Meerakker JB et al.·Eur J Hum Genet

2011

Top 10 resultsSearch PubMed ↗

Recent Gene-Specific Literature

Gene in title · MEDLINE · newest first

Europe PMC

MEGF9 prevents lipopolysaccharide-induced cardiac dysfunction through activating AMPK pathway.

Jin Z et al.·Redox Rep

2025🔓 Open Access

Mendelian randomization analysis and validation supports MEGF9 and MLLT11 as potential targets for the treatment of varicocele and male infertility.

Cai B et al.·Front Endocrinol (Lausanne)

2024🔓 Open Access

miR-7/EGFR/MEGF9 axis regulates cartilage degradation in osteoarthritis via PI3K/AKT/mTOR signaling pathway.

Jiang L et al.·Bioengineered

2021🔓 Open Access

miR-125b acts as a tumor suppressor in breast tumorigenesis via its novel direct targets ENPEP, CK2-α, CCNJ, and MEGF9.

Feliciano A et al.·PLoS One

2013🔓 Open Access

MEGF9: a novel transmembrane protein with a strong and developmentally regulated expression in the nervous system.

Brandt-Bohne U et al.·Biochem J

2007

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Variant Interpretation

Variant interpretation & classification platform

Franklin by Genoox

AI-powered variant curation and clinical analysis

Genomic literature search for variants and genes

ACMG/AMP variant classification tool

Population Databases

Population allele frequencies & constraint metrics

Genomic variants and phenotypes in rare disease patients

Clinical variant interpretations from submitters worldwide

Short genetic variation database

Gene Resources

Gene annotation, transcripts & comparative genomics

Comprehensive gene information and references

Protein sequence, structure and function

Online Mendelian Inheritance in Man

Human gene compendium

Gene expression across human tissues

Expert Curation

Expert-curated gene-disease validity

Gene Curation Coalition — multi-curator classifications

Rare disease encyclopedia and gene-disease associations

Autism-gene association scoring (SFARI)

Gene panels for rare disease diagnostics (Genomics England)

Leiden Open Variation Database — variant listings

Expert-authored summaries of heritable conditions (NCBI)