SRF

Chr 6

serum response factor

Also known as: MCM1

This gene encodes a ubiquitous nuclear protein that stimulates both cell proliferation and differentiation. It is a member of the MADS (MCM1, Agamous, Deficiens, and SRF) box superfamily of transcription factors. This protein binds to the serum response element (SRE) in the promoter region of target genes. This protein regulates the activity of many immediate-early genes, for example c-fos, and thereby participates in cell cycle regulation, apoptosis, cell growth, and cell differentiation. This gene is the downstream target of many pathways; for example, the mitogen-activated protein kinase pathway (MAPK) that acts through the ternary complex factors (TCFs). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

0
ClinVar variants
0
Pathogenic / LP
0.98
pLI score· haploinsufficient
12
Active trials
Clinical SummarySRF
🧬
Gene-Disease Validity (ClinGen)
congenital heart disease · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
0.30LOEUF
pLI 0.975
Z-score 3.45
OE 0.06 (0.020.30)
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.
2.79Z-score
OE missense 0.51 (0.440.59)
131 obs / 256.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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 (0.020.30)
00.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.51 (0.440.59)
00.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
01.21.6
LoF obs/exp: 1 / 15.8Missense obs/exp: 131 / 256.8Syn Z: 0.53

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SRF · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Intracranial MeningiomaRecurrent MeningiomaNF2 Gene Mutation

Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas

RECRUITING
NCT02523014Phase PHASE2Alliance for Clinical Trials in OncologyStarted 2015-09-28
VismodegibFAK Inhibitor GSK2256098Capivasertib
Advanced LymphomaAdvanced Malignant Solid NeoplasmBladder Carcinoma

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ACTIVE NOT RECRUITING
NCT02465060Phase PHASE2National Cancer Institute (NCI)Started 2015-08-17
AdavosertibAfatinibAfatinib Dimaleate
Neovascular Age-related Macular DegenerationDiabetic Macular EdemaRetinal Vein Occlusion

VEGFA-targeting Gene Therapy to Treat Retinal and Choroidal Neovascularization Diseases

ACTIVE NOT RECRUITING
NCT05099094Phase EARLY_PHASE1Shanghai BDgene Co., Ltd.Started 2021-11-25
BD311
Acinar Cell CarcinomaAdenoid Cystic CarcinomaAdrenal Cortical Carcinoma

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

ACTIVE NOT RECRUITING
NCT02834013Phase PHASE2National Cancer Institute (NCI)Started 2017-01-30
Biospecimen CollectionComputed TomographyEchocardiography Test
Stage IB Lung Non-Small Cell Carcinoma AJCC v7Stage II Lung Non-Small Cell Cancer AJCC v7Stage IIA Lung Cancer AJCC v8

Genetic Testing in Screening Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)

ACTIVE NOT RECRUITING
NCT02194738Phase NANational Cancer Institute (NCI)Started 2014-09-26
Biospecimen CollectionCarboplatinCisplatin
Clinical Stage III Cutaneous Melanoma AJCC v8Clinical Stage IV Cutaneous Melanoma AJCC v8Metastatic Cutaneous Melanoma

Physician/Patient Choice of Either High-Dose Recombinant Interferon Alfa-2B or Ipilimumab, Versus Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery

ACTIVE NOT RECRUITING
NCT02506153Phase PHASE3National Cancer Institute (NCI)Started 2015-11-10
Biospecimen CollectionComputed TomographyIpilimumab
Stage II Breast CancerStage IIIA Breast Cancer

Comparison of Axillary Lymph Node Dissection with Axillary Radiation for Patients with Node-Positive Breast Cancer Treated with Chemotherapy

ACTIVE NOT RECRUITING
NCT01901094Phase PHASE3Alliance for Clinical Trials in OncologyStarted 2014-02-24
Axillary Lymph Node Dissection (ALND)Nodal Radiation TherapyAxillary Radiation Therapy
Recurrent Lung Non-Small Cell CarcinomaStage IV Lung Cancer AJCC v8

Comparing Combinations of Targeted Drugs for Advanced Non-Small Cell Lung Cancer That Has EGFR and MET Gene Changes (A Lung-MAP Treatment Trial)

RECRUITING
NCT05642572Phase PHASE2SWOG Cancer Research NetworkStarted 2023-05-05
Biospecimen CollectionCapmatinibComputed Tomography
Castration Levels of TestosteroneMetastatic Prostatic AdenocarcinomaStage IV Prostate Cancer AJCC v8

Standard Systemic Therapy With or Without Definitive Treatment in Treating Participants With Metastatic Prostate Cancer

RECRUITING
NCT03678025Phase PHASE3SWOG Cancer Research NetworkStarted 2018-09-24
AbirateroneBicalutamideDegarelix
Breast Cancer

Evaluating the Addition of Adjuvant Chemotherapy to Ovarian Function Suppression Plus Endocrine Therapy in Premenopausal Patients With pN0-1, ER-Positive/HER2-Negative Breast Cancer and an Oncotype Recurrence Score Less Than or Equal to 25

RECRUITING
NCT05879926Phase PHASE3NRG OncologyStarted 2023-08-31
Ovarian Function Suppression + Aromatase InhibitorAdjuvant Chemotherapy + Ovarian Function Suppression
Melanoma of Unknown PrimaryRecurrent MelanomaStage IIIB Cutaneous Melanoma AJCC v7

Ipilimumab or High-Dose Interferon Alfa-2b in Treating Patients With High-Risk Stage III-IV Melanoma That Has Been Removed by Surgery

ACTIVE NOT RECRUITING
NCT01274338Phase PHASE3National Cancer Institute (NCI)Started 2011-05-25
IpilimumabQuality-of-Life AssessmentRecombinant Interferon Alfa-2b
Breast CancerCognitive Impairments

Cognitive Training for Cancer Related Cognitive Impairment in Breast Cancer Survivors

RECRUITING
NCT05896189Phase NANRG OncologyStarted 2024-04-12
Arm 1: Computerized Cognitive Training-Global Stimulation GamesArm 2: Computerized Cognitive Training-Neuroplasticity Games