MFAP3L

Chr 4

microfibril associated protein 3 like

Also known as: NYD-sp9

NCBI Gene: 9848ENSG00000198948UniProt: O75121

MFAP3L encodes a protein that participates in nuclear signaling pathways involving EGFR and MAPK1/ERK2 and is located at cell junctions, in the nucleoplasm, and at the plasma membrane. The gene is highly constrained against loss-of-function variants (pLI 0.88, LOEUF 0.42), but specific disease associations and inheritance patterns have not yet been established in clinical practice. Further research is needed to define the clinical phenotypes associated with MFAP3L mutations.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
56
P/LP submissions
0%
P/LP missense
0.42
LOEUF
GOF
Mechanism· predicted
Clinical Summary— MFAP3L
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.88) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
56 unique Pathogenic / Likely Pathogenic· 49 VUS of 112 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.42LOEUF
pLI 0.880
Z-score 2.84
OE 0.09 (0.03–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.42Z-score
OE missense 0.74 (0.66–0.84)
181 obs / 243.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.03–0.42)
0≤0.351.4
Missense OE0.74 (0.66–0.84)
0≤0.61.4
Synonymous OE1.07
0≤1.21.6
LoF obs/exp: 1 / 11.3Missense obs/exp: 181 / 243.2Syn Z: -0.56
DN
0.4884th %ile
GOF
0.72top 25%
LOF
0.55top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

112 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic3
VUS49
Likely Benign5
53
Pathogenic
3
Likely Pathogenic
49
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
53
0
53
Likely Pathogenic
0
0
3
0
3
VUS
0
45
4
0
49
Likely Benign
0
4
1
0
5
Benign
0
0
0
0
0
Total049610110

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

View in ClinVar →

Protein Context — Lollipop Plot

MFAP3L · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients