LRCH1

protein-coding

leucine rich repeats and calponin homology domain containing 1

Gene summary

This gene encodes a protein with a leucine-rich repeat and a calponin homology domain. Polymorphism in this gene may be associated with susceptibililty to knee osteoarthritis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2010]

Previous symbols:

CHDC1

MANE transcript

NM_001164211.2

Inheritance

—

ClinVar variants

U:124B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr13:46,553,168-46,753,040

External References & Databases

Ensembl (ENSG00000136141)

Transcript & Mutation Effects

hg38 • Region Span ~199.9 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 LRCH1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 110

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001164211.2. 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		1 clinvar	2
missense			114 clinvar		1 clinvar	115
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	124	0	2	126

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001164211.2	RefSeq	NP_001157683.2	20	MANE Select
ENST00000389797.8	Ensembl	ENSP00000374447.3	20	MANE Select
NM_001164213.2	RefSeq	NP_001157685.2	19	Standard
NM_015116.3	RefSeq	NP_055931.2	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of GTPase activity
cellular response to chemokine
negative regulation of T cell migration

Molecular Function

protein binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000389797
Coding exons: 20
Length: 199873
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 125748
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.39	334	413	0.808	0.0000215	4982
Missense (PolyPhen)		115	174.03	0.6608		2159
Synonymous	0.739	148	160	0.926	0.00000901	1462
Loss of Function	5.18	6	42.5	0.141	0.00000227	491

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0018	0.0019	notable
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a negative regulator of GTPase CDC42 by sequestering CDC42-guanine exchange factor DOCK8. Probably by preventing CDC42 activation, negatively regulates CD4(+) T-cell migration. {ECO:0000269|PubMed:28028151}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.161
RVIS EVS: 0
RVIS percentile EVS: 54.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.672

Gene Damage Prediction

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