NRCAM

neuronal cell adhesion molecule, the group of Ig-like cell adhesion molecule family|Fibronectin type III domain containing|I-set domain containing

Basic information

Region (hg38): 7:108147622-108456717

Links

ENSG00000091129 ∙ NCBI:4897 ∙ OMIM:601581 ∙ HGNC:7994 ∙ Uniprot:Q92823 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with neuromuscular and skeletal abnormalities (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with neuromuscular and skeletal abnormalities (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with neuromuscular and skeletal abnormalities	AR	General	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	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	35108495

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NRCAM gene.

• Inborn genetic diseases (47 variants)
• not provided (13 variants)
• Neurodevelopmental disorder with neuromuscular and skeletal abnormalities (5 variants)
• NRCAM-related disorder (2 variants)
• NRCAM-related condition (1 variants)
• Normal pregnancy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NRCAM gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	3	5
missense			51	3	2	56
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					2	2
Total	0	1	51	5	7

Variants in NRCAM

This is a list of pathogenic ClinVar variants found in the NRCAM region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-108149936-C-T		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
7-108149972-C-T		NRCAM-related disorder	Benign (Jul 31, 2019)
7-108150041-C-A		Inborn genetic diseases	Uncertain significance (Jul 05, 2023)
7-108150043-C-T		Inborn genetic diseases	Uncertain significance (Aug 20, 2023)
7-108150058-A-G		Inborn genetic diseases	Uncertain significance (Oct 06, 2022)
7-108150061-A-C			Uncertain significance (-)
7-108150081-T-C			Benign (Dec 31, 2019)
7-108150109-C-T		Inborn genetic diseases	Uncertain significance (Jul 27, 2022)
7-108150132-G-T		Inborn genetic diseases	Uncertain significance (Dec 02, 2022)
7-108159534-T-C			Likely benign (Mar 29, 2018)
7-108160353-T-C			Likely benign (Apr 06, 2018)
7-108160372-C-T		Inborn genetic diseases	Uncertain significance (Jun 29, 2023)
7-108160421-G-A		Inborn genetic diseases	Uncertain significance (Jan 11, 2023)
7-108160459-T-C		Inborn genetic diseases	Uncertain significance (Jun 16, 2023)
7-108160469-T-A		Inborn genetic diseases	Uncertain significance (May 22, 2023)
7-108160481-G-A		Inborn genetic diseases	Uncertain significance (Feb 11, 2022)
7-108166977-C-A		Inborn genetic diseases	Uncertain significance (Dec 12, 2023)
7-108167034-C-T		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
7-108167037-G-A		Inborn genetic diseases	Uncertain significance (Oct 06, 2021)
7-108168324-T-G		Inborn genetic diseases	Uncertain significance (Jul 26, 2022)
7-108168331-C-T		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
7-108176584-G-A		NRCAM-related disorder	Likely benign (Oct 28, 2019)
7-108176586-C-T		Inborn genetic diseases	Uncertain significance (Jun 21, 2022)
7-108178008-T-C		Inborn genetic diseases	Uncertain significance (Sep 29, 2023)
7-108178039-C-T		NRCAM-related disorder	Likely benign (Jul 11, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NRCAM	protein_coding	protein_coding	ENST00000379028	30	309094

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0153	0.985	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.91	566	709	0.798	0.0000372	8526
Missense in Polyphen		199	305.32	0.65177		3727
Synonymous	1.35	235	263	0.894	0.0000149	2499
Loss of Function	5.74	18	69.8	0.258	0.00000363	854

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000266	0.000266
Ashkenazi Jewish	0.000199	0.0000992
East Asian	0.000285	0.000272
Finnish	0.0000948	0.0000924
European (Non-Finnish)	0.000133	0.000132
Middle Eastern	0.000285	0.000272
South Asian	0.0000993	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cell adhesion protein that is required for normal responses to cell-cell contacts in brain and in the peripheral nervous system. Plays a role in neurite outgrowth in response to contactin binding. Plays a role in mediating cell-cell contacts between Schwann cells and axons. Plays a role in the formation and maintenance of the nodes of Ranvier on myelinated axons. Nodes of Ranvier contain clustered sodium channels that are crucial for the saltatory propagation of action potentials along myelinated axons. During development, nodes of Ranvier are formed by the fusion of two heminodes. Required for normal clustering of sodium channels at heminodes; not required for the formation of mature nodes with normal sodium channel clusters. Required, together with GLDN, for maintaining NFASC and sodium channel clusters at mature nodes of Ranvier. {ECO:0000250|UniProtKB:Q810U4}.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Developmental Biology;NrCAM interactions;Neurofascin interactions;Interaction between L1 and Ankyrins;L1CAM interactions;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.251

Intolerance Scores

• loftool: 0.679
• rvis_EVS: -1.37
• rvis_percentile_EVS: 4.51

Haploinsufficiency Scores

• pHI: 0.486
• hipred: Y
• hipred_score: 0.587
• ghis: 0.604

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.744

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nrcam
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: angiogenesis;neuron migration;axonogenesis;axonal fasciculation;synapse assembly;central nervous system development;protein localization;neuronal action potential propagation;regulation of axon extension;retinal ganglion cell axon guidance;heterotypic cell-cell adhesion;clustering of voltage-gated sodium channels;positive regulation of neuron differentiation;cell-cell adhesion;regulation of postsynapse organization
• Cellular component: extracellular region;plasma membrane;integral component of plasma membrane;external side of plasma membrane;neuron projection;axon initial segment;glutamatergic synapse;integral component of postsynaptic density membrane
• Molecular function: protein binding;ankyrin binding;protein binding involved in heterotypic cell-cell adhesion