LRCH2

protein-coding

leucine rich repeats and calponin homology domain containing 2

Gene summary

This gene encodes a member of the leucine-rich repeat and calponin homology domain-containing protein family. These family members contain multiple N-terminal leucine-rich repeats, in addition to a C-terminal calponin homology domain, a type of domain that mediates interactions with actin filaments. These proteins are conserved across animal species, and studies of a similar Drosophila protein indicate a function as a cytoskeletal scaffolding protein. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2011]

MANE transcript

NM_020871.4

Inheritance

—

ClinVar variants

P:1U:135B:6

Top phenotype

Cerebellar ataxia

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chrX:115,110,616-115,234,096

External References & Databases

Ensembl (ENSG00000130224)

Transcript & Mutation Effects

hg38 • Region Span ~123.5 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 LRCH2 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 342

not providedTotal: 28

Cerebellar ataxiaTotal: 1

Demyelinating peripheral neuropathyTotal: 1

Neurodevelopmental disorderTotal: 1

Kleine-Levin syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020871.4. 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			11 clinvar	3 clinvar		14
missense	1 clinvar		98 clinvar	3 clinvar		102
nonsense			5 clinvar			5
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			21 clinvar			21
Total	1	0	135	6	0	142

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020871.4	RefSeq	NP_065922.3	21	MANE Select
ENST00000317135.13	Ensembl	ENSP00000325091.8	21	MANE Select
NM_001243963.2	RefSeq	NP_001230892.1	20	Standard
ENST00000538422.2	Ensembl	ENSP00000439366.1	20	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000317135
Coding exons: 21
Length: 123451
Individuals with no LoFs: 108989
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 108990
p: 0.00000459

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.94	138	219	0.631	0.0000156	4934
Missense (PolyPhen)		50	98.25	0.50891		2179
Synonymous	1.24	64	77.9	0.822	0.00000524	1427
Loss of Function	4.36	2	26.0	0.0769	0.00000205	578

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00015	0.00012	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0936

Intolerance Scores

RVIS EVS: -0.01
RVIS percentile EVS: 53.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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