MACC1

Chr 7

MET transcriptional regulator MACC1

Also known as: 7A5, SH3BP4L

NCBI Gene: 346389ENSG00000183742UniProt: Q6ZN28

MACC1 is a key regulator of the hepatocyte growth factor (HGF; MIM 142409)-HGF receptor (HGFR, or MET; MIM 164860) pathway, which is involved in cellular growth, epithelial-mesenchymal transition, angiogenesis, cell motility, invasiveness, and metastasis. Expression of MACC1 in colon cancer (MIM 114500) specimens is an independent prognostic indicator for metastasis formation and metastasis-free survival (Stein et al., 2009 [PubMed 19098908]).[supplied by OMIM, Mar 2009]

173
ClinVar variants
37
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MACC1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
37 Pathogenic / Likely Pathogenic· 128 VUS of 173 total submissions
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?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.
1.29LOEUF
pLI 0.000
Z-score 0.28
OE 0.94 (0.70–1.29)
Tolerant

Highly tolerant — LoF variants common in population

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.
-1.29Z-score
OE missense 1.18 (1.09–1.27)
501 obs / 426.1 exp
Tolerant

Tolerant to missense variation

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.0.94 (0.70–1.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.18 (1.09–1.27)
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.0.97
0≤1.21.6
LoF obs/exp: 29 / 30.7Missense obs/exp: 501 / 426.1Syn Z: 0.28

ClinVar Variant Classifications

173 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic2
VUS128
Likely Benign8
35
Pathogenic
2
Likely Pathogenic
128
VUS
8
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
2
0
2
VUS
0
124
4
0
128
Likely Benign
0
8
0
0
8
Benign
0
0
0
0
0
Total0132410173

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

View in ClinVar →

Protein Context — Lollipop Plot

MACC1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Depression accelerates gastric cancer invasion and metastasis by inducing a neuroendocrine phenotype via the catecholamine/β(2) -AR/MACC1 axis.
Pan C et al.·Cancer Commun (Lond)
2021
MACC1 - a novel target for solid cancers.
Stein U·Expert Opin Ther Targets
2013Review
Comprehensive insights into MACC1-AS1: Role in cancer and therapeutic implications.
Liang C et al.·Gene
2025Review
Decoding and targeting the molecular basis of MACC1-driven metastatic spread: Lessons from big data mining and clinical-experimental approaches.
Budczies J et al.·Semin Cancer Biol
2020Review
MACC1 is a potential prognostic biomarker for cancer immunotherapy in lung adenocarcinoma.
Pan C et al.·Carcinogenesis
2025
MACC1-the first decade of a key metastasis molecule from gene discovery to clinical translation.
Radhakrishnan H et al.·Cancer Metastasis Rev
2018Review
Prognostic Value of MACC1 in Digestive System Neoplasms: A Systematic Review and Meta-Analysis.
Wu Z et al.·Biomed Res Int
2015Meta-analysis
Colon cancer metastasis: MACC1 and Met as metastatic pacemakers.
Arlt F et al.·Int J Biochem Cell Biol
2009Review
Metastasis-associated in colon cancer-1 in gastric cancer: Beyond metastasis.
Wu ZZ et al.·World J Gastroenterol
2016Review
MACC1-AS1: An Emerging Star in the Field of Tumor Biology with Bright Futures in Medicine.
Dong L et al.·Mol Cancer Res
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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