LINGO4

protein-coding

leucine rich repeat and Ig domain containing 4, the group of I-set domain containing

Gene summary

Predicted to enable signaling receptor activity. Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

LRRN6D

MANE transcript

NM_001004432.4

Inheritance

ClinVar variants

U:96B:4

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr1:151,800,264-151,805,419

External References & Databases

Ensembl (ENSG00000213171)

Transcript & Mutation Effects

hg38 • Region Span ~5.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LINGO4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 96

not providedTotal: 2

PolymicrogyriaTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001004432.4. 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		1
missense			96 clinvar	3 clinvar		99
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	96	4	0	100

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001004432.4	RefSeq	NP_001004432.1	1	MANE Select
ENST00000368820.4	Ensembl	ENSP00000357810.4	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

extracellular space
integral component of membrane
extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368820
Coding exons: 1
Length: 5891
Individuals with no LoFs: 125585
Homozygous LoFs: 0
Heterozygous LoFs: 163
Defined: 125748
p: 0.000648

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.678	296	331	0.895	0.0000190	3763
Missense (PolyPhen)		109	120.98	0.90099		1492
Synonymous	1.04	128	144	0.890	0.00000737	1401
Loss of Function	1.14	8	12.3	0.649	7.05e-7	126

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00062	0.00062	rare
Latino/Admixed American	0.00043	0.00043	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0034	0.0034	notable
Finnish	0.00046	0.00046	rare
European (Non-Finnish)	0.00037	0.00037	rare
South Asian	0.00062	0.00062	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.268

Intolerance Scores

RVIS EVS: -0.29
RVIS percentile EVS: 33.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.299

Gene Damage Prediction

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