DAPK1

death associated protein kinase 1, the group of Ankyrin repeat domain containing|ROCO family|Death associated protein kinases

Basic information

Region (hg38): 9:87497227-87708634

Links

ENSG00000196730 ∙ NCBI:1612 ∙ OMIM:600831 ∙ HGNC:2674 ∙ Uniprot:P53355 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism spectrum disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DAPK1 gene.

• Inborn genetic diseases (62 variants)
• not provided (29 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DAPK1 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				9	7	16
missense			62	3	1	66
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					4	4
non coding				1	4	5
Total	0	0	62	13	12

Variants in DAPK1

This is a list of pathogenic ClinVar variants found in the DAPK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-87499110-T-C			Likely benign (Oct 23, 2018)
9-87499119-C-T			Likely benign (May 30, 2017)
9-87499130-A-G		not specified	Uncertain significance (Jun 22, 2023)
9-87604973-A-C		not specified	Uncertain significance (Jun 16, 2023)
9-87604982-C-T		not specified	Uncertain significance (Nov 17, 2022)
9-87605052-G-A		not specified	Uncertain significance (Sep 27, 2022)
9-87605066-G-C		not specified	Uncertain significance (Dec 21, 2022)
9-87637937-T-C			Benign (Oct 09, 2018)
9-87637944-G-T		not specified	Uncertain significance (Oct 21, 2021)
9-87637948-C-T		not specified	Uncertain significance (Oct 17, 2023)
9-87638024-A-G			Benign (Dec 31, 2019)
9-87638035-G-A		not specified	Uncertain significance (Sep 20, 2023)
9-87638073-G-C		Myoepithelial tumor	Uncertain significance (Nov 01, 2022)
9-87639461-A-G		not specified	Uncertain significance (Aug 12, 2021)
9-87640307-G-A			Likely benign (Dec 11, 2018)
9-87640366-A-G		not specified	Uncertain significance (Feb 08, 2023)
9-87640437-G-A		not specified	Uncertain significance (Nov 28, 2023)
9-87640793-C-G			Benign (Dec 31, 2019)
9-87640823-T-G		not specified	Uncertain significance (Sep 14, 2023)
9-87641974-A-C		not specified	Uncertain significance (Dec 03, 2021)
9-87643366-T-A			Benign (Dec 31, 2019)
9-87643367-A-T			Likely benign (Dec 31, 2019)
9-87643366-T-TTA			Benign (Dec 31, 2019)
9-87643404-A-G		not specified	Uncertain significance (Aug 02, 2021)
9-87643415-A-G		not specified	Uncertain significance (Jul 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DAPK1	protein_coding	protein_coding	ENST00000408954	25	211406

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00233	124898	0	22	124920	0.0000881

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.57	664	878	0.756	0.0000547	9394
Missense in Polyphen		137	235.52	0.58169		2410
Synonymous	-0.600	386	371	1.04	0.0000256	2824
Loss of Function	6.29	11	66.3	0.166	0.00000347	749

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000158	0.000151
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000556
Finnish	0.0000469	0.0000464
European (Non-Finnish)	0.0000975	0.0000970
Middle Eastern	0.0000556	0.0000556
South Asian	0.000133	0.000131
Other	0.000166	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript- selective translation inhibition.
• Pathway: Bladder cancer - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Bladder Cancer;Caspase activation via extrinsic apoptotic signalling pathway;Apoptosis;Programmed Cell Death;Ligand-independent caspase activation via DCC;IFN-gamma pathway;Netrin-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.291
• rvis_EVS: -1.28
• rvis_percentile_EVS: 5.19

Haploinsufficiency Scores

• pHI: 0.182
• hipred: Y
• hipred_score: 0.639
• ghis: 0.526

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.813

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dapk1
• Phenotype: homeostasis/metabolism phenotype; cellular 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); renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: protein phosphorylation;apoptotic process;extrinsic apoptotic signaling pathway via death domain receptors;regulation of autophagy;positive regulation of autophagy;negative regulation of translation;intracellular signal transduction;regulation of apoptotic process;negative regulation of apoptotic process;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;protein autophosphorylation;cellular response to interferon-gamma;cellular response to hydroperoxide;apoptotic signaling pathway;regulation of NMDA receptor activity
• Cellular component: nucleus;cytoplasm;plasma membrane;actin cytoskeleton
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;calmodulin-dependent protein kinase activity;protein binding;calmodulin binding;ATP binding;GTP binding;syntaxin-1 binding;identical protein binding