PKDCC

protein kinase domain containing, cytoplasmic

Basic information

Region (hg38): 2:42048020-42058517

Links

ENSG00000162878 ∙ NCBI:91461 ∙ OMIM:614150 ∙ HGNC:25123 ∙ Uniprot:Q504Y2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• rhizomelic limb shortening with dysmorphic features (Strong), mode of inheritance: AR
• rhizomelic limb shortening with dysmorphic features (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Rhizomelic limb shortening with dysmorphic features	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	Craniofacial; Musculoskeletal; Neurologic	30478137

ClinVar

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

• not provided (141 variants)
• Inborn genetic diseases (36 variants)
• Rhizomelic limb shortening with dysmorphic features (12 variants)
• Abnormality of the skeletal system (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PKDCC 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			1	33	8	42
missense			85	2	3	90
nonsense		2				2
start loss						0
frameshift	4	3				7
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region			4	3		7
non coding			1	6	2	9
Total	4	7	87	41	13

Highest pathogenic variant AF is 0.00000666

Variants in PKDCC

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

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

Position	Type	Phenotype	Significance	ClinVar
2-42048215-G-A			Uncertain significance (Oct 13, 2023)
2-42048216-C-T			Uncertain significance (Oct 13, 2022)
2-42048246-T-G		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)
2-42048259-C-G			Likely benign (May 22, 2023)
2-42048259-C-T			Likely benign (Dec 05, 2021)
2-42048294-C-T			Uncertain significance (Oct 03, 2023)
2-42048296-C-A			Uncertain significance (Apr 13, 2021)
2-42048310-G-C		Inborn genetic diseases	Uncertain significance (Apr 25, 2022)
2-42048318-A-G		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
2-42048322-T-C			Likely benign (Feb 16, 2023)
2-42048324-C-T			Uncertain significance (Feb 03, 2022)
2-42048331-C-T			Likely benign (Apr 08, 2022)
2-42048336-G-A		Inborn genetic diseases	Uncertain significance (Feb 14, 2023)
2-42048340-G-A			Likely benign (Jul 13, 2022)
2-42048398-G-C			Uncertain significance (Feb 06, 2022)
2-42048403-G-A			Likely benign (Aug 06, 2021)
2-42048408-A-G			Uncertain significance (Feb 10, 2022)
2-42048411-C-T		Inborn genetic diseases	Uncertain significance (Feb 22, 2024)
2-42048421-C-G			Likely benign (Jul 12, 2023)
2-42048424-CGGGCCCGGGG-C			Pathogenic (Oct 05, 2023)
2-42048424-C-CG		Rhizomelic limb shortening with dysmorphic features	Likely pathogenic (Nov 28, 2022)
2-42048464-G-C		Inborn genetic diseases	Uncertain significance (Aug 15, 2022)
2-42048466-C-T			Likely benign (Mar 14, 2023)
2-42048470-G-A			Uncertain significance (Aug 16, 2022)
2-42048475-G-A			Likely benign (Aug 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PKDCC	protein_coding	protein_coding	ENST00000294964	7	10509

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000213	0.911	125734	0	13	125747	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.293	233	221	1.06	0.0000128	3037
Missense in Polyphen		59	63.768	0.92523		735
Synonymous	-0.333	100	95.8	1.04	0.00000565	1086
Loss of Function	1.60	10	17.1	0.584	8.27e-7	200

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000126	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000799	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.0000337	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Secreted tyrosine-protein kinase that mediates phosphorylation of extracellular proteins and endogenous proteins in the secretory pathway, which is essential for patterning at organogenesis stages. Mediates phosphorylation of MMP1, MMP13, MMP14, MMP19 and ERP29 (PubMed:25171405). Probably plays a role in platelets: rapidly and quantitatively secreted from platelets in response to stimulation of platelet degranulation (PubMed:25171405). May also have serine/threonine protein kinase activity. Required for longitudinal bone growth through regulation of chondrocyte differentiation. May be indirectly involved in protein transport from the Golgi apparatus to the plasma membrane (By similarity). {ECO:0000250|UniProtKB:Q5RJI4, ECO:0000269|PubMed:25171405}.

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.229
• ghis: 0.495

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.231

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pkdcc
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; growth/size/body region 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); digestive/alimentary phenotype; limbs/digits/tail phenotype; skeleton phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype

Gene ontology

• Biological process: skeletal system development;protein transport;peptidyl-tyrosine phosphorylation;cell differentiation;bone mineralization;positive regulation of bone mineralization;positive regulation of chondrocyte differentiation;limb morphogenesis;multicellular organism growth;negative regulation of Golgi to plasma membrane protein transport;lung alveolus development;embryonic digestive tract development;roof of mouth development
• Cellular component: extracellular region;Golgi apparatus
• Molecular function: protein kinase activity;non-membrane spanning protein tyrosine kinase activity;ATP binding