KNDC1 (Kinase Non-Catalytic C-Lobe Domain Containing 1)
A brain-enriched Ras guanine nucleotide exchange factor implicated in neuronal development and cognitive function
Gene Information Card
| Symbol | KNDC1 |
|---|---|
| Full Name | Kinase Non-Catalytic C-Lobe Domain Containing 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q26.11 |
| NCBI Gene ID | 85442 ncbi.nlm.nih.gov/gene/85442 |
| Ensembl ID | ENSG00000171798 |
| UniProt ID | Q5TCX7 |
| OMIM ID | 617201 |
| HGNC ID | 28379 |
| Aliases | C10orf46, dJ1033B10.2, KND1 |
Description
KNDC1 encodes a brain-specific Ras guanine nucleotide exchange factor (RasGEF) that activates Ras family small GTPases. It contains a RasGEF domain and a kinase non-catalytic C-lobe domain. The protein is predominantly expressed in neurons and plays a role in dendrite outgrowth, neuronal migration, and synaptic plasticity. Mutations in KNDC1 have been associated with autosomal recessive intellectual disability and developmental delay.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal recessive 70 | Loss-of-function mutations impair Ras signaling in neurons, leading to reduced dendritic arborization | PMID: 28965846; ClinVar |
| Developmental delay with or without seizures | Homozygous truncating variants disrupt protein function, affecting neuronal development | ClinVar; OMIM #617201 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Cerebral cortex | 15.2 | High |
| Cerebellum | 10.8 | High |
| Hippocampus | 14.1 | High |
| Testis | 1.2 | Low |
| Other tissues | <1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.5 | Neuronal model |
| U-87 MG (glioblastoma) | 6.2 | Glial origin |
| HEK293 (embryonic kidney) | 0.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.226C>T (p.Arg76*) | Nonsense | Rare | Loss of function; truncation of RasGEF domain |
| c.1042_1043del (p.Leu348Glufs*3) | Frameshift | Rare | Loss of function; premature termination |
| c.1546G>A (p.Gly516Arg) | Missense | Unknown | Likely damaging; affects conserved residue |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift variants leading to premature stop codons or protein truncation are classified as loss-of-function.
Gain of Function (GOF)
No gain-of-function mutations have been reported for KNDC1.
Dominant Negative (DN)
No dominant-negative mutations have been described.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ras signaling pathway (Reactome: R-HSA-167044)
• Signaling by Rho GTPases (Reactome: R-HSA-194315)
Protein Summary
KNDC1 is a 1,320-amino-acid protein containing an N-terminal RasGEF domain and a C-terminal kinase non-catalytic C-lobe domain. It is expressed almost exclusively in the brain, where it localizes to dendrites and synapses. The protein activates Ras and downstream MAPK/ERK signaling, promoting dendritic growth and neuronal connectivity. Loss of KNDC1 function leads to impaired neuronal development and is linked to autosomal recessive intellectual disability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KNDC1 Knockout HEK293 Cell Line | EDJ-KQ10357 | Human | 85442 | Details Get a Quote |
| KNDC1 Knockout A-549 Cell Line | EDJ-KQ37678 | Human | 85442 | Details Get a Quote |
| KNDC1 Knockout HCT 116 Cell Line | EDJ-KQ37679 | Human | 85442 | Details Get a Quote |
| KNDC1 Knockout HeLa Cell Line | EDJ-KQ57714 | Human | 85442 | Details Get a Quote |
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