LMCD1

protein-coding

LIM and cysteine rich domains 1, the group of LIM domain containing

Gene summary

This gene encodes a member of the LIM-domain family of zinc finger proteins. The encoded protein contains an N-terminal cysteine-rich domain and two C-terminal LIM domains. The presence of LIM domains suggests involvement in protein-protein interactions. The protein may act as a co-regulator of transcription along with other transcription factors. Alternate splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

MANE transcript

NM_014583.4

Inheritance

—

ClinVar variants

U:70B:6

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr3:8,501,807-8,574,668

External References & Databases

Ensembl (ENSG00000071282)

Transcript & Mutation Effects

hg38 • Region Span ~72.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LMCD1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014583.4. 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			1 clinvar	2 clinvar		3
missense			65 clinvar	4 clinvar		69
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	70	6	0	76

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014583.4	RefSeq	NP_055398.1	6	MANE Select
ENST00000157600.8	Ensembl	ENSP00000157600.3	6	MANE Select
NM_001278233.2	RefSeq	NP_001265162.1	4	Standard
NM_001278234.2	RefSeq	NP_001265163.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
lmcd1	Danio rerio	Structure: atrioventricular valve Quality: functionality abnormal

Gene / Model

Organism

Observed Phenotype

lmcd1

Danio rerio

Structure: atrioventricular valve

Quality: functionality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Surfactant metabolism
Metabolism of proteins

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of cardiac muscle hypertrophy
cellular protein metabolic process
positive regulation of calcineurin-NFAT signaling cascade

Molecular Function

transcription corepressor activity
zinc ion binding

Cellular Component

nucleus
nucleoplasm
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000157600
Coding exons: 6
Length: 66413
Individuals with no LoFs: 125726
Homozygous LoFs: 1
Heterozygous LoFs: 21
Defined: 125748
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.660	207	236	0.879	0.0000148	2372
Missense (PolyPhen)		72	92.19	0.781		933
Synonymous	1.28	77	92.6	0.831	0.00000614	710
Loss of Function	2.31	8	18.8	0.425	9.60e-7	210

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00011	0.000097	rare
South Asian	0.00017	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional cofactor that restricts GATA6 function by inhibiting DNA-binding, resulting in repression of GATA6 transcriptional activation of downstream target genes. Represses GATA6-mediated trans activation of lung- and cardiac tissue- specific promoters. Inhibits DNA-binding by GATA4 and GATA1 to the cTNC promoter (By similarity). Plays a critical role in the development of cardiac hypertrophy via activation of calcineurin/nuclear factor of activated T-cells signaling pathway. {ECO:0000250, ECO:0000269|PubMed:20026769}.;

Recessive Scores

pRec: 0.114

Intolerance Scores

LoFtool: 0.193
RVIS EVS: -0.18
RVIS percentile EVS: 40.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.881

Gene Damage Prediction

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