KALRN

kalirin RhoGEF kinase, the group of MicroRNA protein coding host genes|Fibronectin type III domain containing|I-set domain containing|Dbl family Rho GEFs

Basic information

Region (hg38): 3:124033368-124726325

Previous symbols: [ "HAPIP" ]

Links

ENSG00000160145 ∙ NCBI:8997 ∙ OMIM:604605 ∙ HGNC:4814 ∙ Uniprot:O60229 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• not provided (20 variants)
• Inborn genetic diseases (8 variants)
• not specified (2 variants)
• KALRN-related condition (1 variants)
• Coronary heart disease, susceptibility to, 5 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KALRN 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				5	7	12
missense			11	2	4	17
nonsense				1		1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding						0
Total	0	0	11	8	11

Variants in KALRN

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

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

Position	Type	Phenotype	Significance	ClinVar
3-124055231-T-G		Coronary heart disease, susceptibility to, 5 • KALRN-related disorder	Benign (Feb 22, 2021)
3-124228048-G-A		KALRN-related disorder	Benign (Nov 18, 2019)
3-124269108-T-C		KALRN-related disorder	Likely benign (Jul 16, 2019)
3-124269180-C-T			Likely benign (Dec 01, 2022)
3-124269192-T-C		KALRN-related disorder	Benign (Sep 24, 2019)
3-124325992-A-T		not specified	Uncertain significance (Oct 26, 2021)
3-124326012-C-T			Likely benign (Dec 01, 2022)
3-124326102-C-T		KALRN-related disorder	Benign (Apr 27, 2021)
3-124329917-C-T		KALRN-related disorder	Benign (Nov 25, 2019)
3-124329929-C-T		KALRN-related disorder	Likely benign (Sep 09, 2019)
3-124334472-G-A		not specified	Benign (May 04, 2022)
3-124347234-AGAGGCATGATGACTTTGAAGAGGTGGCTCAGGTGAGAAGCTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTCTAGATGAGG-A		KALRN-related disorder	Likely benign (Dec 29, 2022)
3-124395221-G-A		KALRN-related disorder	Benign (Oct 21, 2019)
3-124395236-G-A		KALRN-related disorder	Benign (Jun 03, 2019)
3-124398702-C-T		Coronary heart disease, susceptibility to, 5	Uncertain significance (Jan 01, 2019)
3-124398868-C-T		KALRN-related disorder	Likely benign (Jun 07, 2019)
3-124422974-A-G		not specified	Uncertain significance (Aug 17, 2021)
3-124434441-C-T		KALRN-related disorder	Likely benign (Jul 01, 2019)
3-124434444-C-T		KALRN-related disorder	Likely benign (Apr 15, 2019)
3-124438959-G-A		KALRN-related disorder	Benign (Dec 27, 2019)
3-124446215-T-C		not specified	Uncertain significance (Sep 16, 2021)
3-124446759-A-T		KALRN-related disorder	Benign (May 27, 2019)
3-124455274-C-A			Uncertain significance (Sep 30, 2022)
3-124456663-G-C		not specified	Uncertain significance (Jun 22, 2021)
3-124456678-C-T		KALRN-related disorder	Likely benign (Aug 27, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KALRN	protein_coding	protein_coding	ENST00000240874	34	646303

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.00e-10	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.36	590	973	0.607	0.0000593	10992
Missense in Polyphen		108	254.12	0.42499		2918
Synonymous	-0.0284	392	391	1.00	0.0000240	3113
Loss of Function	8.26	8	94.7	0.0845	0.00000469	1037

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000919	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.000109	0.000109
South Asian	0.0000667	0.0000653
Other	0.000326	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Promotes the exchange of GDP by GTP. Activates specific Rho GTPase family members, thereby inducing various signaling mechanisms that regulate neuronal shape, growth, and plasticity, through their effects on the actin cytoskeleton. Induces lamellipodia independent of its GEF activity. {ECO:0000269|PubMed:10023074}.
• Disease: DISEASE: Coronary heart disease 5 (CHDS5) [MIM:608901]: A multifactorial disease characterized by an imbalance between myocardial functional requirements and the capacity of the coronary vessels to supply sufficient blood flow. Decreased capacity of the coronary vessels is often associated with thickening and loss of elasticity of the coronary arteries. {ECO:0000269|PubMed:17357071}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Developmental Biology;Signaling by GPCR;Signal Transduction;MAPK6/MAPK4 signaling;EPH-Ephrin signaling;EPHB-mediated forward signaling;Rho GTPase cycle;Signaling by Rho GTPases;Regulation of RAC1 activity;NRAGE signals death through JNK;MAPK family signaling cascades;Death Receptor Signalling;p75 NTR receptor-mediated signalling;Axon guidance;G alpha (12/13) signalling events;G alpha (q) signalling events;GPCR downstream signalling;EPHB forward signaling;Cell death signalling via NRAGE, NRIF and NADE;Arf6 downstream pathway (Consensus)

Intolerance Scores

• loftool: 0.415
• rvis_EVS: -3.65
• rvis_percentile_EVS: 0.27

Haploinsufficiency Scores

• pHI: 0.667
• hipred: Y
• hipred_score: 0.639
• ghis: 0.516

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.780

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kalrn
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; muscle phenotype; normal phenotype; 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); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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)

Zebrafish Information Network

• Gene name: kalrna
• Affected structure: thrombocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: protein phosphorylation;signal transduction;G protein-coupled receptor signaling pathway;nervous system development;neuromuscular junction development;lactation;memory;adult locomotory behavior;vesicle-mediated transport;regulation of Rho protein signal transduction;social behavior;intracellular signal transduction;maternal behavior;positive regulation of apoptotic process;positive regulation of GTPase activity;habituation;ephrin receptor signaling pathway;regulation of small GTPase mediated signal transduction;negative regulation of growth hormone secretion;maternal process involved in parturition;positive regulation of dendritic spine morphogenesis
• Cellular component: nucleoplasm;cytosol;actin cytoskeleton;extracellular exosome
• Molecular function: protein serine/threonine kinase activity;guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;GTPase activator activity;ATP binding;metal ion binding