PKDCC

protein-coding

protein kinase domain containing, cytoplasmic

Gene summary

Enables non-membrane spanning protein tyrosine kinase activity. Involved in peptidyl-tyrosine phosphorylation and skeletal system development. Located in extracellular region. Implicated in intrinsic asthma. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_138370.3

Inheritance

ClinVar variants

P:22U:156B:81

Top phenotype

Rhizomelic limb shortening with dysmorphic features

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr2:42,048,021-42,058,517

External References & Databases

Ensembl (ENSG00000162878)

Transcript & Mutation Effects

hg38 • Region Span ~10.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

rhizomelic limb shortening with dysmorphic featuresMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032935

Submitter: G2P

rhizomelic limb shortening with dysmorphic featuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032935

Submitter: Ambry Genetics

rhizomelic limb shortening with dysmorphic featuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032935

Submitter: Labcorp Genetics (formerly Invitae)

rhizomelic limb shortening with dysmorphic featuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032935

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Rhizomelic limb shortening with dysmorphic featuresAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 30478137

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PKDCC variants in ClinVar

8 Conditions Cataloged

not providedTotal: 194

Inborn genetic diseasesTotal: 114

Rhizomelic limb shortening with dysmorphic featuresTotal: 12

PKDCC-related disorderTotal: 7

not specifiedTotal: 3

Skeletal dysplasiaTotal: 1

Fetal anomalies with a likely genetic causeTotal: 1

Abnormality of the skeletal systemTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138370.3. 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			2 clinvar	67 clinvar	5 clinvar	74
missense		1 clinvar	150 clinvar	7 clinvar	2 clinvar	160
nonsense	2 clinvar	2 clinvar	1 clinvar			5
start loss						0
frameshift	11 clinvar	3 clinvar				14
splice donor/acceptor (+/-2bp)		3 clinvar	3 clinvar			6
Total	13	9	156	74	7	259

Highest pathogenic variant AF is 0.000012408687

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138370.3	RefSeq	NP_612379.2	7	MANE Select
ENST00000294964.6	Ensembl	ENSP00000294964.5	7	MANE Select
ENST00000401498.6	Ensembl	ENSP00000385220.2	3	Standard
ENST00000914294.1	Ensembl	ENSP00000584353.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

skeletal system development
protein transport
peptidyl-tyrosine phosphorylation
cell differentiation
bone mineralization

Molecular Function

protein kinase activity
non-membrane spanning protein tyrosine kinase activity
ATP binding

Cellular Component

extracellular region
Golgi apparatus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000294964
Coding exons: 7
Length: 10509
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125747
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.293	233	221	1.06	0.0000128	3037
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000068	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.000034	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.231

Gene Damage Prediction

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