MFHAS1

Chr 8

multifunctional ROCO family signaling regulator 1

Also known as: LRRC65, MASL1, ROCO4

NCBI Gene: 9258ENSG00000147324UniProt: Q9Y4C4

Identified in a human 8p amplicon, this gene is a potential oncogene whose expression is enhanced in some malignant fibrous histiocytomas (MFH). The primary structure of its product includes an ATP/GTP-binding site, three leucine zipper domains, and a leucine-rich tandem repeat, which are structural or functional elements for interactions among proteins related to the cell cycle, and which suggest that overexpression might be oncogenic with respect to MFH. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Malignant fibrous histiocytomaMIM #605352
0
Active trials
84
Pathogenic / LP
270
ClinVar variants
3
Pubs (1 yr)
-1.9
Missense Z
0.82
LOEUF
Clinical Summary— MFHAS1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
84 Pathogenic / Likely Pathogenic· 163 VUS of 270 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.82LOEUF
pLI 0.000
Z-score 2.36
OE 0.56 (0.39–0.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.94Z-score
OE missense 1.22 (1.15–1.29)
757 obs / 620.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.56 (0.39–0.82)
0≤0.351.4
Missense OE1.22 (1.15–1.29)
0≤0.61.4
Synonymous OE1.43
0≤1.21.6
LoF obs/exp: 19 / 33.8Missense obs/exp: 757 / 620.8Syn Z: -5.73
GOFDN
DN
0.6356th %ile
GOF
0.7126th %ile
LOF
0.2678th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction 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

270 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic81
Likely Pathogenic3
VUS163
Likely Benign18
Benign5
81
Pathogenic
3
Likely Pathogenic
163
VUS
18
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
81
0
81
Likely Pathogenic
0
0
3
0
3
VUS
0
151
12
0
163
Likely Benign
0
4
4
10
18
Benign
0
0
0
5
5
Total015510015270

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

View in ClinVar →

MFHAS1 · 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
Landmark / reviewRecent case evidence
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
Genetic Loci Associated With Periodontitis: The FinnGen Study Based on National Health Registers.
Salminen A et al.·J Clin Periodontol
2025
Mutational, immune microenvironment, and clinicopathological profiles of diffuse large B-cell lymphoma and follicular lymphoma with BCL6 rearrangement.
Carreras J et al.·Virchows Arch
2024
MFHAS1 suppresses TLR4 signaling pathway via induction of PP2A C subunit cytoplasm translocation and inhibition of c-Jun dephosphorylation at Thr239.
Shi Q et al.·Mol Immunol
2017
Whole exome sequencing of relapsed/refractory patients expands the repertoire of somatic mutations in diffuse large B-cell lymphoma.
Mareschal S et al.·Genes Chromosomes Cancer
2016Cohort
Quantile-Dependent Heritability of Glucose, Insulin, Proinsulin, Insulin Resistance, and Glycated Hemoglobin.
Williams PT·Lifestyle Genom
2022
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Silencing MFHAS1 Induces Pyroptosis via the JNK-activated NF-κB/Caspase1/ GSDMD Signal Axis in Breast Cancer.
Jin Y et al.·Curr Pharm Des
2023
Effects of MFHAS1 on cognitive impairment and dendritic pathology in the hippocampus of septic rats.
Zhong J et al.·Life Sci
2019
Correction: Ubiquitylation of MFHAS1 by the ubiquitin ligase praja2 promotes M1 macrophage polarization by activating JNK and p38 pathways.
Zhong J et al.·Cell Death Dis
2018Open Access
Identification of ST3AGL4, MFHAS1, CSNK2A2 and CD226 as loci associated with systemic lupus erythematosus (SLE) and evaluation of SLE genetics in drug repositioning.
Wang YF et al.·Ann Rheum Dis
2018
High Glucose Stimulates Expression of MFHAS1 to Mitigate Inflammation via Akt/HO-1 Pathway in Human Umbilical Vein Endothelial Cells.
Wang HH et al.·Inflammation
2018
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