DIPK2B

Summary

DIPK2B (divergent protein kinase domain 2B, HGNC:25866) is a protein-coding gene on chromosome Xp11.3, encoding Divergent protein kinase domain 2B (Q9H7Y0).

Predicted to be located in extracellular region.

Source: NCBI Gene 79742 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 60 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_176819

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25866
Approved symbol	DIPK2B
Name	divergent protein kinase domain 2B
Location	Xp11.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14103, DIA1R
Ensembl gene	ENSG00000147113
Ensembl biotype	protein_coding
OMIM	300959
Entrez	79742

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000377934, ENST00000398000, ENST00000477281, ENST00000492138, ENST00000905163, ENST00000905164

RefSeq mRNA: 2 — MANE Select: NM_176819 NM_024689, NM_176819

CCDS: CCDS14266, CCDS48096

Canonical transcript exons

ENST00000398000 — 5 exons

Exon	Start	End
ENSE00000978773	45191751	45192015
ENSE00001324692	45153910	45154198
ENSE00001475573	45157715	45157888
ENSE00001552345	45148373	45151992
ENSE00003843327	45200594	45200876

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 91.80.

FANTOM5 (CAGE): breadth broad, TPM avg 7.0193 / max 296.7787, expressed in 317 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199015	6.3803	314
199016	0.2169	114
199017	0.1819	102
199013	0.0985	46
199018	0.0942	67
199014	0.0474	33

Top tissues by expression

260 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
omental fat pad	UBERON:0010414	91.80	gold quality
peritoneum	UBERON:0002358	91.73	gold quality
apex of heart	UBERON:0002098	90.93	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.51	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.24	gold quality
smooth muscle tissue	UBERON:0001135	88.22	gold quality
body of uterus	UBERON:0009853	88.22	gold quality
tendon of biceps brachii	UBERON:0008188	87.32	silver quality
endocervix	UBERON:0000458	87.11	gold quality
sural nerve	UBERON:0015488	87.00	gold quality
left uterine tube	UBERON:0001303	86.33	gold quality
right lobe of thyroid gland	UBERON:0001119	86.20	gold quality
heart left ventricle	UBERON:0002084	85.55	gold quality
diaphragm	UBERON:0001103	85.37	gold quality
adipose tissue	UBERON:0001013	85.07	gold quality
cardiac ventricle	UBERON:0002082	85.02	gold quality
left lobe of thyroid gland	UBERON:0001120	84.85	gold quality
mucosa of stomach	UBERON:0001199	84.73	gold quality
connective tissue	UBERON:0002384	84.13	gold quality
upper lobe of left lung	UBERON:0008952	84.07	gold quality
thyroid gland	UBERON:0002046	84.00	gold quality
ectocervix	UBERON:0012249	83.70	gold quality
upper lobe of lung	UBERON:0008948	83.30	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.29	gold quality
lower esophagus	UBERON:0013473	83.25	gold quality
type B pancreatic cell	CL:0000169	83.16	gold quality
tibial nerve	UBERON:0001323	83.06	gold quality
olfactory bulb	UBERON:0002264	83.01	gold quality
gall bladder	UBERON:0002110	82.99	gold quality
myometrium	UBERON:0001296	82.70	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-8271	yes	522.74
E-MTAB-10287	yes	319.99
E-MTAB-6701	yes	32.55
E-HCAD-1	yes	30.76
E-ANND-3	yes	29.06
E-MTAB-8410	yes	20.26
E-MTAB-6678	yes	13.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

84 targeting DIPK2B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 1)

• results support a model where the DIA1 and DIA1R regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-like symptoms and/or mental retardation (PMID:21264219)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dipk2b	ENSDARG00000061747
mus_musculus	Dipk2b	ENSMUSG00000037358
rattus_norvegicus	Dipk2b	ENSRNOG00000004265
drosophila_melanogaster	CG11170	FBGN0034705

Paralogs (1): DIPK2A (ENSG00000181744)

Protein

Protein identifiers

Divergent protein kinase domain 2B — Q9H7Y0 (reviewed: Q9H7Y0)

Alternative names: Deleted in autism-related protein 1

All UniProt accessions (1): Q9H7Y0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Disease relevance. Genetic variations in CXorf36 may be associated with susceptibility to autism.

Similarity. Belongs to the DIPK family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H7Y0-1	1	yes
Q9H7Y0-2	2

RefSeq proteins (2): NP_078965, NP_789789* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020519	DIPK2A/B	Family
IPR022049	FAM69_kinase_dom	Domain

Pfam: PF12260

UniProt features (7 total): splice variant 2, sequence variant 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H7Y0-F1	84.17	0.65

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 100

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 59 (showing top): EFC_Q6, MODULE_256, TGGAAA_NFAT_Q4_01, MODULE_166, WGTTNNNNNAAA_UNKNOWN, NFAT_Q6, HNF4ALPHA_Q6, HATADA_METHYLATED_IN_LUNG_CANCER_UP, chrXp11, GATA1_05, RYBP_TARGET_GENES, MIR12136, MIR4261, MIR147B_5P, MIR5003_5P

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DIPK2B	DIPK1C	Q0P6D2	724
DIPK2B	DIPK1A	Q5T7M9	657
DIPK2B	DIPK1B	Q5VUD6	572
DIPK2B	POMK	Q9H5K3	509
DIPK2B	CXorf66	Q5JRM2	506
DIPK2B	DUSP21	Q9H596	480
DIPK2B	PKDCC	Q504Y2	479
DIPK2B	RRP12	Q5JTH9	476
DIPK2B	LRATD2	Q96KN1	428
DIPK2B	FAM20A	Q96MK3	424
DIPK2B	GSDMC	Q9BYG8	414
DIPK2B	RAPGEF5	Q92565	412
DIPK2B	KRABD4	Q5JUW0	397
DIPK2B	TCEANC	Q8N8B7	373
DIPK2B	PPP1R2C	O14990	371

IntAct

0 interactions, top by confidence:

BioGRID (2): CXorf36 (Affinity Capture-MS), CXorf36 (Positive Genetic)

ESM2 similar proteins: A0JPE1, A4D0V7, D3Z2R5, O43916, P97259, Q08834, Q09328, Q1RLQ5, Q3TUA9, Q4V8A9, Q58CX7, Q5F349, Q5FVL3, Q5HZP7, Q5NDE4, Q5NDE5, Q5NDE7, Q5NDE8, Q5R634, Q5R9Q9, Q5RJQ0, Q5T7M9, Q5U3W1, Q5VUD6, Q640M6, Q68CR1, Q6DBY9, Q6DCL6, Q6Q2W4, Q80TS8, Q8C1F4, Q8C3I9, Q8N6G5, Q8NBP0, Q8NHY0, Q8R4G6, Q8R553, Q8WTR4, Q92179, Q95JJ0

Diamond homologs: B1H2T2, Q3USZ8, Q58CX7, Q8C3I9, Q8NDZ4, Q9H7Y0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

60 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	16
Likely benign	8
Benign	6

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1180516	GRCh37/hg19 Xp11.4-11.3(chrX:42069104-45843277)x1	Pathogenic
635966	Single allele	Pathogenic
183367	NC_000023.10:g.(?43479884)(45501849_?)del	Likely pathogenic

SpliceAI

1051 predictions. Top by Δscore:

Variant	Effect	Δscore
X:45151662:T:C	donor_gain	1.0000
X:45153906:GTACC:G	donor_loss	1.0000
X:45153907:TAC:T	donor_loss	1.0000
X:45153908:ACCTT:A	donor_gain	1.0000
X:45153909:C:CG	donor_loss	1.0000
X:45153909:CCTTC:C	donor_gain	1.0000
X:45153912:T:A	donor_gain	1.0000
X:45157711:ATACC:A	donor_loss	1.0000
X:45157712:TACCT:T	donor_loss	1.0000
X:45157713:A:AT	donor_loss	1.0000
X:45151716:AGGGG:A	donor_gain	0.9900
X:45153871:T:A	donor_gain	0.9900
X:45154208:C:CT	acceptor_gain	0.9900
X:45154209:A:T	acceptor_gain	0.9900
X:45157710:CATA:C	donor_loss	0.9900
X:45157887:CC:C	acceptor_gain	0.9900
X:45157888:CC:C	acceptor_gain	0.9900
X:45191746:CTCA:C	donor_loss	0.9900
X:45191747:TCA:T	donor_loss	0.9900
X:45191748:CA:C	donor_loss	0.9900
X:45191749:A:C	donor_loss	0.9900
X:45191750:C:T	donor_loss	0.9900
X:45151661:AT:A	donor_gain	0.9800
X:45151839:C:A	donor_gain	0.9800
X:45151993:C:CC	acceptor_gain	0.9800
X:45153872:C:A	donor_gain	0.9800
X:45153904:GAGTA:G	donor_loss	0.9800
X:45153909:CCTT:C	donor_gain	0.9800
X:45200505:T:TA	donor_gain	0.9800
X:45149349:C:CC	acceptor_gain	0.9700

AlphaMissense

2822 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:45154177:A:G	W232R	0.998
X:45154177:A:T	W232R	0.998
X:45157839:C:G	R183P	0.998
X:45151674:C:G	C427S	0.997
X:45151675:A:T	C427S	0.997
X:45154175:C:A	W232C	0.997
X:45154175:C:G	W232C	0.997
X:45157758:A:G	L210P	0.996
X:45157827:C:G	R187P	0.996
X:45151675:A:G	C427R	0.995
X:45157833:A:T	V185D	0.995
X:45200634:C:A	G65W	0.995
X:45151674:C:T	C427Y	0.994
X:45154059:A:G	L271P	0.994
X:45191770:A:T	L160H	0.994
X:45191789:A:G	W154R	0.994
X:45191789:A:T	W154R	0.994
X:45151674:C:A	C427F	0.993
X:45200621:C:T	C69Y	0.993
X:45200633:C:T	G65E	0.993
X:45200640:A:G	C63R	0.993
X:45200648:C:G	C60S	0.993
X:45200649:A:T	C60S	0.993
X:45151673:G:C	C427W	0.992
X:45151686:C:G	R423P	0.992
X:45151870:A:G	C362R	0.992
X:45154149:C:T	C241Y	0.992
X:45157746:A:G	L214P	0.992
X:45157799:G:C	S196R	0.992
X:45157799:G:T	S196R	0.992

dbSNP variants (sampled 300 via entrez): RS1000015820 (X:45174940 G>A), RS1000054423 (X:45161114 A>G), RS1000203805 (X:45186130 C>T), RS1000297403 (X:45165371 C>T), RS1000358348 (X:45191629 C>G), RS1000380980 (X:45153011 G>C), RS1000427062 (X:45197059 A>G), RS1000507826 (X:45175637 A>G), RS1000561617 (X:45176073 C>T), RS1000585672 (X:45184191 G>A), RS1000618345 (X:45167413 G>T), RS1000661877 (X:45194407 G>A), RS1000713700 (X:45194911 CT>C,CTT), RS1000977617 (X:45183614 C>T), RS1001060478 (X:45159235 C>A)

Disease associations

OMIM: gene MIM:300959 | disease phenotypes: MIM:300867

GenCC curated gene-disease

Mondo (3): Kabuki syndrome 2 (MONDO:0010465), intellectual disability (MONDO:0001071), skeletal dysplasia (MONDO:0018230)

Orphanet (3): Kabuki syndrome (Orphanet:2322), Primary bone dysplasia (Orphanet:364526), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases mutagenesis	3
bisphenol A	affects cotreatment, increases methylation	1
bisphenol S	decreases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Silicon Dioxide	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

203 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders