MYOCD

protein-coding

myocardin, the group of Myocardin family

Gene summary

This gene encodes a nuclear protein, which is expressed in heart, aorta, and in smooth muscle cell-containing tissues. It functions as a transcriptional co-activator of serum response factor (SRF) and modulates expression of cardiac and smooth muscle-specific SRF-target genes, and thus may play a crucial role in cardiogenesis and differentiation of the smooth muscle cell lineage. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

MANE transcript

NM_001146312.3

Inheritance

AR, AD

ClinVar variants

P:10U:151B:33

Top phenotype

Megabladder, congenital

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr17:12,665,890-12,768,949

External References & Databases

Ensembl (ENSG00000141052)

Transcript & Mutation Effects

hg38 • Region Span ~103.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

megabladder, congenitalSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032879

Submitter: PanelApp Australia

megabladder, congenitalLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0032879

Submitter: Labcorp Genetics (formerly Invitae)

megabladder, congenitalLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0032879

Submitter: Labcorp Genetics (formerly Invitae)

megabladder, congenitalSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032879

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Megabladder, congenitalAD

Manifestation: Genitourinary; Renal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 31513549

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYOCD variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 148

not providedTotal: 27

Megabladder, congenitalTotal: 19

MYOCD-related conditionTotal: 11

Prune belly syndromeTotal: 2

Prostate cancerTotal: 1

SeizureTotal: 1

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001146312.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	9 clinvar	5 clinvar	16
missense		1 clinvar	139 clinvar	14 clinvar	5 clinvar	159
nonsense	3 clinvar		3 clinvar			6
start loss						0
frameshift	2 clinvar	1 clinvar	5 clinvar			8
splice donor/acceptor (+/-2bp)	1 clinvar	2 clinvar	2 clinvar			5
Total	6	4	151	23	10	194

Highest pathogenic variant AF is 0.000009578426

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001146312.3	RefSeq	NP_001139784.1	14	MANE Select
ENST00000425538.6	Ensembl	ENSP00000401678.1	14	MANE Select
NM_001378306.1	RefSeq	NP_001365235.1	11	Standard
NM_153604.4	RefSeq	NP_705832.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

SRF and miRs in Smooth Muscle Differentiation and Proliferation
PDGFR-beta signaling pathway

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of cell growth by extracellular stimulus
vasculogenesis
response to hypoxia
cardiac ventricle development

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription activator activity, RNA polymerase II-specific
transcription coactivator activity
protein binding
transcription factor binding

Cellular Component

nuclear chromatin
nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000425538
Coding exons: 14
Length: 103060
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125748
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.336	517	539	0.959	0.0000281	6463
Missense (PolyPhen)		197	214.38	0.91894		2654
Synonymous	-1.28	251	227	1.11	0.0000136	1975
Loss of Function	4.73	10	43.8	0.228	0.00000245	468

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000089	0.000088	rare
South Asian	0.000043	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Smooth muscle cells (SM) and cardiac muscle cells- specific transcriptional factor which uses the canonical single or multiple CArG boxes DNA sequence. Acts as a cofactor of serum response factor (SRF) with the potential to modulate SRF-target genes. Plays a crucial role in cardiogenesis and differentiation of the smooth muscle cell lineage (myogenesis) (By similarity). {ECO:0000250, ECO:0000269|PubMed:12640126}.;

Recessive Scores

pRec: 0.216

Intolerance Scores

LoFtool: 0.0234
RVIS EVS: -0.68
RVIS percentile EVS: 15.39

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.653

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium