KNDC1

protein-coding

kinase non-catalytic C-lobe domain containing 1

Gene summary

The protein encoded by this gene is a Ras guanine nucleotide exchange factor that appears to negatively regulate dendritic growth in the brain. Knockdown of this gene in senescent umbilical vein endothelial cells partially reversed the senescence, showing that this gene could potentially be targeted by anti-aging therapies. [provided by RefSeq, Dec 2016]

Previous symbols:

RASGEF2
C10orf23

MANE transcript

NM_152643.8

Inheritance

—

ClinVar variants

U:333B:42

Top phenotype

Breast ductal adenocarcinoma

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr10:133,160,219-133,226,412

External References & Databases

Ensembl (ENSG00000171798)

Transcript & Mutation Effects

hg38 • Region Span ~66.2 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 KNDC1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 347

not providedTotal: 21

Breast ductal adenocarcinomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152643.8. 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			5 clinvar	4 clinvar	2 clinvar	11
missense			326 clinvar	30 clinvar	6 clinvar	362
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	333	34	8	375

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152643.8	RefSeq	NP_689856.6	30	MANE Select
ENST00000304613.8	Ensembl	ENSP00000304437.3	30	MANE Select
NM_001347864.2	RefSeq	NP_001334793.1	3	Standard
NM_001347865.2	RefSeq	NP_001334794.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of protein phosphorylation
small GTPase mediated signal transduction
biological_process
cerebellar granule cell differentiation
regulation of dendrite morphogenesis

Molecular Function

molecular_function
Ras guanyl-nucleotide exchange factor activity

Cellular Component

cellular_component
dendrite
guanyl-nucleotide exchange factor complex
neuronal cell body
perikaryon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000304613
Coding exons: 30
Length: 65966
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125748
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.894	968	1.05e+3	0.922	0.0000704	11130
Missense (PolyPhen)		158	196.99	0.80206		2064
Synonymous	-0.0699	498	496	1.00	0.0000387	3618
Loss of Function	5.76	20	73.1	0.274	0.00000354	836

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000099	0.000092	rare
European (Non-Finnish)	0.00015	0.00014	rare
South Asian	0.00011	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: RAS-Guanine nucleotide exchange factor (GEF) that controls the negative regulation of neuronal dendrite growth by mediating a signaling pathway linking RAS and MAP2 (By similarity). May be involved in cellular senescence (PubMed:24788352). {ECO:0000250|UniProtKB:Q0KK55, ECO:0000269|PubMed:24788352}.;

Recessive Scores

pRec: 0.0955

Intolerance Scores

LoFtool: 0.522
RVIS EVS: 1.09
RVIS percentile EVS: 91.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.155

Gene Damage Prediction

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