CAPZA2

Summary

CAPZA2 (capping actin protein of muscle Z-line subunit alpha 2, HGNC:1490) is a protein-coding gene on chromosome 7q31.2, encoding F-actin-capping protein subunit alpha-2 (P47755). F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends.

The protein encoded by this gene is a member of the F-actin capping protein alpha subunit family. It is the alpha subunit of the barbed-end actin binding protein Cap Z. By capping the barbed end of actin filaments, Cap Z regulates the growth of the actin filaments at the barbed end.

Source: NCBI Gene 830 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Moderate, GenCC)
• GWAS associations: 14
• Clinical variants (ClinVar): 66 total — 2 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_006136

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1490
Approved symbol	CAPZA2
Name	capping actin protein of muscle Z-line subunit alpha 2
Location	7q31.2
Locus type	gene with protein product
Status	Approved
Aliases	CAPZ, CAPPA2
Ensembl gene	ENSG00000198898
Ensembl biotype	protein_coding
OMIM	601571
Entrez	830

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 10 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000361183, ENST00000414148, ENST00000417431, ENST00000426421, ENST00000449080, ENST00000461878, ENST00000464223, ENST00000464669, ENST00000465607, ENST00000466023, ENST00000484325, ENST00000490693, ENST00000496161, ENST00000903570, ENST00000903571, ENST00000903572, ENST00000920349, ENST00000943391, ENST00000943392

RefSeq mRNA: 1 — MANE Select: NM_006136 NM_006136

CCDS: CCDS5768

Canonical transcript exons

ENST00000361183 — 10 exons

Exon	Start	End
ENSE00001759595	116862587	116862650
ENSE00001903963	116917727	116922049
ENSE00003462292	116898772	116898835
ENSE00003468394	116916060	116916122
ENSE00003601807	116888127	116888190
ENSE00003618726	116906263	116906342
ENSE00003621068	116912069	116912140
ENSE00003621973	116904177	116904383
ENSE00003645990	116910233	116910311
ENSE00003646588	116892994	116893045

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 95.1048 / max 1972.2218, expressed in 1826 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80686	69.9851	1819
80685	21.7594	1802
80684	3.2404	1433
80681	0.0966	13
80682	0.0157	8
80680	0.0076	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.15	gold quality
monocyte	CL:0000576	99.03	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.95	gold quality
biceps brachii	UBERON:0001507	98.92	gold quality
heart right ventricle	UBERON:0002080	98.91	gold quality
mononuclear cell	CL:0000842	98.87	gold quality
blood vessel layer	UBERON:0004797	98.81	gold quality
calcaneal tendon	UBERON:0003701	98.72	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.67	gold quality
leukocyte	CL:0000738	98.66	gold quality
myocardium	UBERON:0002349	98.66	gold quality
cauda epididymis	UBERON:0004360	98.65	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.65	gold quality
germinal epithelium of ovary	UBERON:0001304	98.64	gold quality
diaphragm	UBERON:0001103	98.61	gold quality
islet of Langerhans	UBERON:0000006	98.59	gold quality
jejunum	UBERON:0002115	98.49	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.49	gold quality
cortical plate	UBERON:0005343	98.46	gold quality
lower lobe of lung	UBERON:0008949	98.46	gold quality
adrenal tissue	UBERON:0018303	98.46	gold quality
colonic mucosa	UBERON:0000317	98.43	gold quality
vastus lateralis	UBERON:0001379	98.40	gold quality
superficial temporal artery	UBERON:0001614	98.37	gold quality
visceral pleura	UBERON:0002401	98.31	gold quality
gall bladder	UBERON:0002110	98.25	gold quality
skeletal muscle tissue	UBERON:0001134	98.24	gold quality
palpebral conjunctiva	UBERON:0001812	98.22	gold quality
endometrium	UBERON:0001295	98.21	gold quality
seminal vesicle	UBERON:0000998	98.20	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	37.35
E-HCAD-4	yes	29.95
E-MTAB-6701	yes	18.43
E-MTAB-6386	no	460.53
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

120 targeting CAPZA2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-497-5P	99.92	71.83	2674

Literature-anchored findings (GeneRIF, showing 3)

• Variants in CAPZA2, a member of an F-actin capping complex, cause intellectual disability and developmental delay. (PMID:32338762)
• Capping protein regulates endosomal trafficking by controlling F-actin density around endocytic vesicles and recruiting RAB5 effectors. (PMID:34796874)
• Heterozygous CAPZA2 mutations cause global developmental delay, hypotonia with epilepsy: a case report and the literature review. (PMID:38374166)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Capza2	ENSMUSG00000015733
rattus_norvegicus	Capza2	ENSRNOG00000056207
drosophila_melanogaster	cpa	FBGN0034577
caenorhabditis_elegans		WBGENE00000292

Paralogs (2): CAPZA1 (ENSG00000116489), CAPZA3 (ENSG00000177938)

Protein

Protein identifiers

F-actin-capping protein subunit alpha-2 — P47755 (reviewed: P47755)

Alternative names: CapZ alpha-2

All UniProt accessions (7): P47755, A4D0V4, C9J7V0, C9JCZ4, C9JUG7, F8W9N7, F8WED3

UniProt curated annotations — full annotation on UniProt →

Function. F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments.

Subunit / interactions. Component of the F-actin capping complex, composed of a heterodimer of an alpha and a beta subunit. Component of the WASH complex, composed of F-actin-capping protein subunit alpha (CAPZA1, CAPZA2 or CAPZA3), F-actin-capping protein subunit beta (CAPZB), WASH (WASHC1, WASH2P, WASH3P, WASH4P, WASH5P or WASH6P), WASHC2 (WASHC2A or WASHC2C), WASHC3, WASHC4 and WASHC5. Interacts with RCSD1/CAPZIP. Directly interacts with CRACD; this interaction decreases binding to actin.

Similarity. Belongs to the F-actin-capping protein alpha subunit family.

Isoforms (2)

UniProt ID	Names	Canonical?
P47755-1	1	yes
P47755-2	2

RefSeq proteins (1): NP_006127* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002189	CapZ_alpha	Family
IPR017865	F-actin_cap_asu_CS	Conserved_site
IPR037282	CapZ_alpha/beta	Homologous_superfamily
IPR042276	CapZ_alpha/beta_2	Homologous_superfamily
IPR042489	CapZ_alpha_1	Homologous_superfamily

Pfam: PF01267

UniProt features (6 total): modified residue 2, splice variant 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P47755-F1	93.11	0.85

Functional residue map

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

Post-translational modifications (2): 2, 9

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-2132295	MHC class II antigen presentation
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811436	COPI-independent Golgi-to-ER retrograde traffic
R-HSA-879415	Advanced glycosylation endproduct receptor signaling
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-109582	Hemostasis
R-HSA-1280218	Adaptive Immune System
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-2262752	Cellular responses to stress
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
R-HSA-8856688	Golgi-to-ER retrograde transport
R-HSA-8953897	Cellular responses to stimuli
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9659379	Sensory processing of sound
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 267 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GTCTACC_MIR379, GOBP_BARBED_END_ACTIN_FILAMENT_CAPPING, DITTMER_PTHLH_TARGETS_UP, TATTATA_MIR374, GOBP_NEGATIVE_REGULATION_OF_ACTIN_FILAMENT_DEPOLYMERIZATION, REACTOME_MEMBRANE_TRAFFICKING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (4): actin cytoskeleton organization (GO:0030036), barbed-end actin filament capping (GO:0051016), protein-containing complex assembly (GO:0065003), actin filament capping (GO:0051693)

GO Molecular Function (3): actin filament binding (GO:0051015), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), cytosol (GO:0005829), brush border (GO:0005903), F-actin capping protein complex (GO:0008290), actin cytoskeleton (GO:0015629), membrane (GO:0016020), cortical cytoskeleton (GO:0030863), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Immune System	2
Membrane Trafficking	2
Adaptive Immune System	1
Cellular responses to stress	1
ER to Golgi Anterograde Transport	1
Golgi-to-ER retrograde transport	1
Innate Immune System	1
Sensory processing of sound	1
Hemostasis	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Cellular responses to stimuli	1
Post-translational protein modification	1
Metabolism of proteins	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoskeleton	2
cytoskeleton organization	1
actin filament-based process	1
actin filament capping	1
cellular component assembly	1
protein-containing complex organization	1
negative regulation of actin filament depolymerization	1
negative regulation of actin filament polymerization	1
actin binding	1
protein-containing complex binding	1
cytoskeletal protein binding	1
binding	1
cytoplasm	1
microvillus	1
apical part of cell	1
cluster of actin-based cell projections	1
actin cytoskeleton	1
protein-containing complex	1
cell cortex	1
extracellular vesicle	1

Protein interactions and networks

STRING

2270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAPZA2	CAPZB	P47756	991
CAPZA2	TPPP	O94811	896
CAPZA2	TMOD4	Q9NZQ9	888
CAPZA2	NEB	P20929	875
CAPZA2	ACTR10	Q9NZ32	833
CAPZA2	ACTR3C	Q9C0K3	822
CAPZA2	DCTN2	Q13561	822
CAPZA2	DCTN1	Q14203	816
CAPZA2	TMOD1	P28289	815
CAPZA2	ACTR3B	Q9P1U1	810
CAPZA2	TMOD3	Q9NYL9	798
CAPZA2	TMOD2	Q9NZR1	793
CAPZA2	DCTN5	Q9BTE1	749
CAPZA2	WNT2	P09544	713
CAPZA2	CD2AP	Q9Y5K6	687

IntAct

208 interactions, top by confidence:

A	B	Type	Score
DCTN1	DCTN6	psi-mi:“MI:0914”(association)	0.780
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
DCTN2	DCTN6	psi-mi:“MI:0914”(association)	0.730
DCTN2	DCTN3	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640
CAPZB	CNOT1	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
DCTN5	DCTN6	psi-mi:“MI:0914”(association)	0.640
CNOT7	CAPZA2	psi-mi:“MI:0914”(association)	0.640
Dctn2	DCTN6	psi-mi:“MI:0914”(association)	0.560
DAPK1	MYO1B	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
ATF3	MYL6B	psi-mi:“MI:0914”(association)	0.530
WASHC3	WASH3P	psi-mi:“MI:0914”(association)	0.530
DCTN6	ZBTB43	psi-mi:“MI:0914”(association)	0.530

BioGRID (626): CAPZA2 (Affinity Capture-MS), CAPZA2 (Affinity Capture-MS), CAPZA2 (Affinity Capture-MS), CAPZA2 (Affinity Capture-MS), CAPZA2 (Affinity Capture-MS), CAPZA2 (Affinity Capture-MS), CD2AP (Affinity Capture-MS), ACTR1B (Affinity Capture-MS), ACTR1A (Affinity Capture-MS), ARAP1 (Affinity Capture-MS), CNOT3 (Affinity Capture-MS), KIAA1671 (Affinity Capture-MS), MTCL1 (Affinity Capture-MS), CNOT10 (Affinity Capture-MS), CNOT1 (Affinity Capture-MS)

ESM2 similar proteins: A0M8R8, A0M8S9, A0M8V0, A0PFK5, A1X151, A4D7Q3, A4D7S9, A4FUA8, B2GUZ5, P13127, P25229, P28497, P47753, P47754, P47755, P47757, P52907, P79136, Q00PJ7, Q07DV7, Q07DY0, Q07DZ0, Q07E00, Q07E23, Q07E36, Q07E47, Q09YH6, Q09YJ9, Q09YL0, Q09YN4, Q108U5, Q29221, Q2IBA7, Q2IBB9, Q2IBE7, Q2QL78, Q2QL88, Q2QL99, Q2QLA8, Q2QLB9

Diamond homologs: A0M8R8, A0M8S9, A0M8V0, A0PFK5, A1X151, A4D7Q3, A4D7S9, A4FUA8, B2GUZ5, O82631, P13022, P13127, P25229, P28495, P28497, P34685, P47753, P47754, P47755, P52907, P70190, P9WF01, Q00PJ7, Q07DV7, Q07DY0, Q07DZ0, Q07E00, Q07E23, Q07E36, Q07E47, Q09YH6, Q09YJ9, Q09YL0, Q09YN4, Q108U5, Q29221, Q2IBA7, Q2IBB9, Q2IBE7, Q2QL78

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 197 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by RAS mutants	5	17.6×	5e-04
Parasite infection	5	14.4×	1e-03
Leishmania phagocytosis	5	14.4×	1e-03
COPI-independent Golgi-to-ER retrograde traffic	8	13.8×	4e-05
Signaling by high-kinase activity BRAF mutants	5	13.2×	1e-03
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	8	12.9×	4e-05
Sensory processing of sound	5	12.9×	2e-03
Oncogenic MAPK signaling	6	12.4×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of microtubule polymerization	6	25.8×	9e-05
nuclear-transcribed mRNA poly(A) tail shortening	5	25.6×	6e-04
retrograde transport, endosome to Golgi	7	9.2×	3e-03
actin filament organization	9	6.8×	3e-03
endocytosis	9	5.5×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	47
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
155346	GRCh38/hg38 7q31.1-31.2(chr7:114389395-117253741)x1	Pathogenic
830217	NM_006136.3(CAPZA2):c.766A>G (p.Lys256Glu)	Pathogenic
3369411	NM_006136.3(CAPZA2):c.775C>T (p.Arg259Cys)	Likely pathogenic

SpliceAI

1618 predictions. Top by Δscore:

Variant	Effect	Δscore
7:116862647:GAAG:G	donor_gain	1.0000
7:116862648:AAGGT:A	donor_loss	1.0000
7:116862649:AGGTA:A	donor_loss	1.0000
7:116862650:GGT:G	donor_loss	1.0000
7:116862651:G:GA	donor_loss	1.0000
7:116862651:G:GG	donor_gain	1.0000
7:116888119:T:A	acceptor_gain	1.0000
7:116888124:CAGGT:C	acceptor_loss	1.0000
7:116888126:GGT:G	acceptor_gain	1.0000
7:116888126:GGTGC:G	acceptor_gain	1.0000
7:116888187:AATGG:A	donor_loss	1.0000
7:116888188:ATGG:A	donor_loss	1.0000
7:116888191:G:GG	donor_gain	1.0000
7:116888191:G:T	donor_loss	1.0000
7:116888192:T:A	donor_loss	1.0000
7:116888193:GAGTG:G	donor_loss	1.0000
7:116893046:G:GG	donor_gain	1.0000
7:116897575:G:GT	donor_gain	1.0000
7:116898768:TTA:T	acceptor_loss	1.0000
7:116898769:TA:T	acceptor_loss	1.0000
7:116898770:A:AG	acceptor_gain	1.0000
7:116898770:AGT:A	acceptor_gain	1.0000
7:116898771:G:GA	acceptor_gain	1.0000
7:116898771:GT:G	acceptor_gain	1.0000
7:116898771:GTG:G	acceptor_gain	1.0000
7:116898771:GTGC:G	acceptor_gain	1.0000
7:116898771:GTGCA:G	acceptor_gain	1.0000
7:116898831:ATCAG:A	donor_loss	1.0000
7:116898832:TCAGG:T	donor_loss	1.0000
7:116898833:CAG:C	donor_loss	1.0000

AlphaMissense

1904 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:116888158:C:A	A24D	1.000
7:116888160:C:A	P25T	1.000
7:116888161:C:A	P25H	1.000
7:116888164:C:A	P26H	1.000
7:116888166:G:A	G27R	1.000
7:116888166:G:C	G27R	1.000
7:116888167:G:A	G27E	1.000
7:116888167:G:T	G27V	1.000
7:116892997:T:A	V36D	1.000
7:116893000:G:C	R37P	1.000
7:116893006:T:C	L39P	1.000
7:116893017:G:C	D43H	1.000
7:116893018:A:T	D43V	1.000
7:116893027:T:A	L46H	1.000
7:116893027:T:C	L46P	1.000
7:116898790:C:A	N58K	1.000
7:116898790:C:G	N58K	1.000
7:116904184:T:A	I76K	1.000
7:116906307:C:G	C157W	1.000
7:116906323:T:C	F163L	1.000
7:116906325:C:A	F163L	1.000
7:116906325:C:G	F163L	1.000
7:116910236:T:A	N170K	1.000
7:116910236:T:G	N170K	1.000
7:116910237:G:C	G171R	1.000
7:116910238:G:A	G171D	1.000
7:116910238:G:T	G171V	1.000
7:116910241:G:C	R172P	1.000
7:116910243:T:A	W173R	1.000
7:116910243:T:C	W173R	1.000

dbSNP variants (sampled 300 via entrez): RS1000062727 (7:116867650 CTCGGCTCACTGCA>C), RS1000098302 (7:116918625 T>C), RS1000118673 (7:116886682 C>A), RS1000152473 (7:116868627 G>A), RS1000253332 (7:116900804 T>A,C), RS1000257730 (7:116862386 A>G), RS1000273270 (7:116904986 A>AG), RS1000289062 (7:116862148 G>A), RS1000339984 (7:116873519 TCTC>T), RS1000426263 (7:116900444 G>A,T), RS1000479256 (7:116866944 A>G), RS1000500720 (7:116911108 C>T), RS1000567691 (7:116913525 T>C), RS1000633024 (7:116914901 T>C), RS1000634199 (7:116892626 CAA>C)

Disease associations

OMIM: gene MIM:601571 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Moderate	Autosomal dominant

Mondo (3): neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST004599_57	Mean platelet volume	7.000000e-13
GCST004603_43	Platelet count	9.000000e-13
GCST004607_158	Plateletcrit	5.000000e-11
GCST004616_190	Platelet distribution width	9.000000e-23
GCST005956_17	Waist-to-hip ratio adjusted for BMI	5.000000e-09
GCST005962_49	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-07
GCST007096_87	Pulse pressure	2.000000e-09
GCST010173_115	Triglyceride levels	8.000000e-12
GCST010244_130	Triglyceride levels	2.000000e-13
GCST012489_4	Heel bone mineral density x serum urate levels interaction	2.000000e-11
GCST90002395_697	Mean platelet volume	1.000000e-27
GCST90002400_48	Plateletcrit	3.000000e-15
GCST90002401_467	Platelet distribution width	4.000000e-46
GCST90002402_28	Platelet count	2.000000e-34

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0005763	pulse pressure measurement
EFO:0004530	triglyceride measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066889 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.62	Kd	2384	nM	CHEMBL5653589
5.60	ED50	2531	nM	CHEMBL5653589
5.52	Kd	3042	nM	CHEMBL3752910
5.49	ED50	3230	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147996: Binding affinity to human CAPZA2 incubated for 45 mins by Kinobead based pull down assay	kd	2.3841	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147996: Binding affinity to human CAPZA2 incubated for 45 mins by Kinobead based pull down assay	kd	3.0423	uM

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
perfluorooctane sulfonic acid	decreases expression	2
Air Pollutants	increases abundance, decreases expression, affects expression	2
Doxorubicin	affects expression, increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
coumarin	increases phosphorylation	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	increases expression	1
Aspirin	increases expression	1
Cisplatin	decreases expression, decreases reaction	1
Dactinomycin	affects cotreatment, increases secretion	1
Dinitrochlorobenzene	affects binding	1
Gold	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651038	Binding	Binding affinity to human CAPZA2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 hybrid cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C528	5-8F	Hybrid cell line
CVCL_S665	5-8F/Erbitux	Hybrid cell line

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
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
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
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
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
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)
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development