NCAPH

Summary

NCAPH (non-SMC condensin I complex subunit H, HGNC:1112) is a protein-coding gene on chromosome 2q11.2, encoding Condensin complex subunit 2 (Q15003). Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. It is a common-essential gene (DepMap: required in 97.8% of cancer cell lines).

This gene encodes a member of the barr gene family and a regulatory subunit of the condensin complex. This complex is required for the conversion of interphase chromatin into condensed chromosomes. The protein encoded by this gene is associated with mitotic chromosomes, except during the early phase of chromosome condensation. During interphase, the protein has a distinct punctate nucleolar localization. Alternatively spliced transcript variants encoding different proteins have been described.

Source: NCBI Gene 23397 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly 23, primary, autosomal recessive (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 152 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 6
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 97.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_015341

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1112
Approved symbol	NCAPH
Name	non-SMC condensin I complex subunit H
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	CAP-H, hCAP-H, NCAPH1
Ensembl gene	ENSG00000121152
Ensembl biotype	protein_coding
OMIM	602332
Entrez	23397

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 15 protein_coding, 1 retained_intron

ENST00000240423, ENST00000427946, ENST00000435349, ENST00000435975, ENST00000455200, ENST00000456906, ENST00000477409, ENST00000894500, ENST00000894501, ENST00000928321, ENST00000928322, ENST00000928323, ENST00000928324, ENST00000928325, ENST00000928326, ENST00000928327

RefSeq mRNA: 4 — MANE Select: NM_015341 NM_001281710, NM_001281711, NM_001281712, NM_015341

CCDS: CCDS2021, CCDS62960

Canonical transcript exons

ENST00000240423 — 18 exons

Exon	Start	End
ENSE00000770606	96369425	96369500
ENSE00000770607	96368972	96369063
ENSE00000770608	96365876	96366058
ENSE00000770609	96364481	96364591
ENSE00000770610	96360588	96360710
ENSE00000770619	96341642	96341894
ENSE00000820568	96359045	96359193
ENSE00000820569	96360143	96360249
ENSE00000820570	96367257	96367373
ENSE00001154337	96373292	96377091
ENSE00001893240	96335766	96335848
ENSE00003492999	96353306	96353397
ENSE00003563081	96344105	96344229
ENSE00003564727	96354183	96354388
ENSE00003602184	96342756	96342848
ENSE00003648879	96351831	96352020
ENSE00003650085	96343166	96343304
ENSE00003653556	96342050	96342140

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 95.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.7800 / max 238.7978, expressed in 1451 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21458	19.7800	1451

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	95.24	gold quality
ganglionic eminence	UBERON:0004023	90.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.12	gold quality
left testis	UBERON:0004533	86.79	gold quality
right testis	UBERON:0004534	86.68	gold quality
testis	UBERON:0000473	85.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.89	gold quality
secondary oocyte	CL:0000655	84.49	gold quality
sperm	CL:0000019	83.79	silver quality
mucosa of transverse colon	UBERON:0004991	82.89	gold quality
embryo	UBERON:0000922	82.67	gold quality
rectum	UBERON:0001052	79.38	gold quality
oocyte	CL:0000023	79.19	gold quality
bone marrow cell	CL:0002092	78.73	gold quality
bone marrow	UBERON:0002371	78.70	gold quality
stromal cell of endometrium	CL:0002255	78.26	gold quality
vermiform appendix	UBERON:0001154	77.72	gold quality
lower esophagus mucosa	UBERON:0035834	75.94	gold quality
lymph node	UBERON:0000029	75.93	gold quality
esophagus mucosa	UBERON:0002469	75.48	gold quality
bone element	UBERON:0001474	74.22	gold quality
caecum	UBERON:0001153	71.37	gold quality
adrenal tissue	UBERON:0018303	69.92	gold quality
trabecular bone tissue	UBERON:0002483	69.62	gold quality
endometrium epithelium	UBERON:0004811	68.45	gold quality
spleen	UBERON:0002106	67.93	gold quality
transverse colon	UBERON:0001157	67.17	gold quality
tonsil	UBERON:0002372	67.03	gold quality
adult organism	UBERON:0007023	66.50	gold quality
smooth muscle tissue	UBERON:0001135	66.46	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	9.59
E-ANND-3	yes	5.20
E-GEOD-99795	no	157.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

100 targeting NCAPH, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-3679-3P	99.64	69.88	1599

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 19)

• Our results identify a SSB-specific response of condensin I through PARP-1 and demonstrate a role for condensin in SSB. repair. (PMID:16543152)
• Caspase-3-mediated degradation of condensin Cap-H regulates mitotic cell death. (PMID:21151026)
• NCAPH high expression promotes colonic cancerous cell proliferation. (PMID:28300828)
• miR-199a/b-3p was significantly downregulated in metastatic castration-resistant compared with hormone-sensitive prostate cancer tissues. Ectopic expression of miR-199a/b inhibited cancer cell aggressiveness. The gene coding for NCAPH was directly regulated by miR-199a/b-3p. High expression of NCAPH was significantly associated with poor disease-free survival by The Cancer Genome Atlas database analysis. (PMID:30818424)
• Findings indicate that non-SMC condensing I complex subunit H (NCAPH) could serve as a prognostic biomarker and a potential therapeutic target for patients with hepatocellular carcinoma (HCC). (PMID:31523845)
• Overexpression of MYBL2 promotes proliferation and migration of non-small-cell lung cancer via upregulating NCAPH. (PMID:32200471)
• NCAPH knockdown inhibited cell proliferation, induced cell-cycle arrest at G2/M phase, and prevented colony formation, migration and invasion by NSCLC cells. (PMID:32487618)
• NCAPH is upregulated in endometrial cancer and associated with poor clinicopathologic characteristics. (PMID:32628282)
• NCAPH is negatively associated with Mcl1 in nonsmall cell lung cancer. (PMID:32945371)
• Identification of NCAPH as a biomarker for prognosis of breast cancer. (PMID:33009967)
• HPV E7-mediated NCAPH ectopic expression regulates the carcinogenesis of cervical carcinoma via PI3K/AKT/SGK pathway. (PMID:33311486)
• miR-133b targets NCAPH to promote beta-catenin degradation and reduce cancer stem cell maintenance in non-small cell lung cancer. (PMID:34230450)
• NCAPH regulates gastric cancer progression through DNA damage response. (PMID:34962823)
• NCAPH promotes cell proliferation and inhibits cell apoptosis of bladder cancer cells through MEK/ERK signaling pathway. (PMID:34974790)
• NCAPH is a prognostic biomarker and associated with immune infiltrates in lung adenocarcinoma. (PMID:35688915)
• NCAPH Stabilizes GEN1 in Chromatin to Resolve Ultra-Fine DNA Bridges and Maintain Chromosome Stability. (PMID:36380731)
• Non-SMC condensin I complex subunit H participates in anti-programmed cell death-1 resistance of clear cell renal cell carcinomas. (PMID:36642844)
• An integrative pan-cancer analysis reveals the carcinogenic effects of NCAPH in human cancer. (PMID:36650758)
• MiR-1976/NCAPH/P65 axis inhibits the malignant phenotypes of lung adenocarcinoma. (PMID:38755247)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ncaph	ENSDARG00000061468
mus_musculus	Ncaph	ENSMUSG00000034906
rattus_norvegicus	Ncaph	ENSRNOG00000012051
drosophila_melanogaster	barr	FBGN0014127

Protein

Protein identifiers

Condensin complex subunit 2 — Q15003 (reviewed: Q15003)

Alternative names: Barren homolog protein 1, Chromosome-associated protein H, Non-SMC condensin I complex subunit H, XCAP-H homolog

All UniProt accessions (5): C9J470, C9JZP1, E9PHA2, Q15003, H7C415

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size.

Subunit / interactions. Component of the condensin complex, which contains the SMC2 and SMC4 heterodimer, and three non SMC subunits that probably regulate the complex: NCAPH/BRRN1, NCAPD2/CAPD2 and NCAPG.

Subcellular location. Nucleus. Cytoplasm. Chromosome.

Tissue specificity. Widely expressed at low level. Expressed in proliferating cells.

Post-translational modifications. Phosphorylated by CDK1. Its phosphorylation, as well as that of NCAPD2 and NCAPG subunits, activates the condensin complex and is required for chromosome condensation.

Disease relevance. Microcephaly 23, primary, autosomal recessive (MCPH23) [MIM:617985] A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CND2 (condensin subunit 2) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15003-1	1	yes
Q15003-2	2

RefSeq proteins (4): NP_001268639, NP_001268640, NP_001268641, NP_056156* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022816	Condensin_barren_su2	Family

Pfam: PF05786

UniProt features (30 total): modified residue 18, region of interest 3, helix 3, sequence variant 2, chain 1, cross-link 1, splice variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6IGX	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15003-F1	60.16	0.08

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 (19): 78, 81, 87, 89, 92, 96, 201, 233, 432, 496, 598, 605, 637, 488, 15, 25, 28, 49, 70

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2514853	Condensation of Prometaphase Chromosomes

MSigDB gene sets: 347 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, CROONQUIST_NRAS_SIGNALING_DN, GEORGES_CELL_CYCLE_MIR192_TARGETS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_CHROMOSOME_SEPARATION, MODULE_308, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, KONG_E2F3_TARGETS, GOBP_CHROMOSOME_CONDENSATION, GOLDRATH_ANTIGEN_RESPONSE, LI_WILMS_TUMOR_ANAPLASTIC_UP

GO Biological Process (10): mitotic chromosome condensation (GO:0007076), meiotic chromosome condensation (GO:0010032), cell division (GO:0051301), female meiosis chromosome separation (GO:0051309), positive regulation of chromosome segregation (GO:0051984), positive regulation of chromosome separation (GO:1905820), positive regulation of chromosome condensation (GO:1905821), female meiotic nuclear division (GO:0007143), chromosome condensation (GO:0030261), meiotic chromosome segregation (GO:0045132)

GO Molecular Function (2): chromatin binding (GO:0003682), protein binding (GO:0005515)

GO Cellular Component (8): condensed nuclear chromosome (GO:0000794), condensin complex (GO:0000796), nucleoplasm (GO:0005654), cytosol (GO:0005829), membrane (GO:0016020), nucleus (GO:0005634), chromosome (GO:0005694), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Mitotic Prometaphase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
chromosome condensation	3
meiotic cell cycle	2
positive regulation of cell cycle process	2
meiotic nuclear division	2
binding	2
mitotic sister chromatid segregation	1
mitotic cell cycle	1
mitotic cell cycle process	1
chromosome organization involved in meiotic cell cycle	1
cellular process	1
female meiotic nuclear division	1
female meiosis chromosome segregation	1
meiotic chromosome separation	1
chromosome segregation	1
regulation of chromosome segregation	1
chromosome separation	1
regulation of chromosome separation	1
regulation of chromosome condensation	1
positive regulation of chromosome organization	1
female gamete generation	1
chromosome organization	1
nuclear chromosome segregation	1
meiotic cell cycle process	1
nuclear chromosome	1
condensed chromosome	1
nucleus	1
chromosome	1
protein-containing complex	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2188 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NCAPH	NCAPD2	Q15021	998
NCAPH	NCAPG	Q9BPX3	996
NCAPH	SMC4	Q9NTJ3	996
NCAPH	SMC2	O95347	911
NCAPH	NCAPD3	P42695	908
NCAPH	NCAPG2	Q86XI2	864
NCAPH	RAD21	O60216	852
NCAPH	POU3F3	P20264	778
NCAPH	NCAPH2	Q6IBW4	777
NCAPH	KIF14	Q15058	653
NCAPH	TTK	P33981	652
NCAPH	AURKB	Q96GD4	650
NCAPH	TPX2	Q9ULW0	629
NCAPH	KIF4A	O95239	622
NCAPH	KIF20A	O95235	621

IntAct

107 interactions, top by confidence:

A	B	Type	Score
ARPC1A	ARPC2	psi-mi:“MI:0914”(association)	0.900
NCAPH	SMC2	psi-mi:“MI:0915”(physical association)	0.810
NCAPH	NCAPG	psi-mi:“MI:0915”(physical association)	0.780
NCAPG	NCAPH	psi-mi:“MI:0915”(physical association)	0.780
NCAPH	NCAPD2	psi-mi:“MI:0915”(physical association)	0.720
NCAPH	SMC4	psi-mi:“MI:0915”(physical association)	0.720
NCAPD2	NCAPH	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
FZD10	NRP1	psi-mi:“MI:0914”(association)	0.530
KLKB1	NCAPH	psi-mi:“MI:0914”(association)	0.530
DPEP1	ILVBL	psi-mi:“MI:0914”(association)	0.530
GPR137B	DOC2A	psi-mi:“MI:0914”(association)	0.530
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530

BioGRID (399): NCAPH (Affinity Capture-MS), NCAPH (Affinity Capture-MS), NCAPH (Affinity Capture-MS), NCAPH (Affinity Capture-MS), NCAPH (Affinity Capture-MS), NCAPH (Affinity Capture-MS), NCAPH (Affinity Capture-MS), NCAPH (Co-fractionation), NCAPH (Co-fractionation), NCAPH (Co-fractionation), SMC2 (Co-fractionation), NCAPH (Affinity Capture-MS), NCAPH (Proximity Label-MS), NCAPH (Proximity Label-MS), NCAPH (Proximity Label-MS)

ESM2 similar proteins: A0A1P8AW69, A2AU37, A5LFW4, A6QPC8, B2ZX90, D2HSB3, F4HY56, F4I1T7, F4JET1, F4K3G5, O04539, O13067, O48686, P36626, Q0P4S5, Q0WPK4, Q15003, Q19325, Q28GV1, Q564K3, Q5RH01, Q641G4, Q66IH2, Q67W65, Q6A331, Q6A332, Q6A333, Q6AUQ7, Q8C156, Q8GSA7, Q8W1Y0, Q9C689, Q9C7C4, Q9FFH1, Q9FKV5, Q9FLL1, Q9FQ19, Q9FQ20, Q9FT92, Q9H4I0

Diamond homologs: O13067, Q15003, Q8C156

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NCAPH	“form complex”	“Condensin I”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 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.

GO biological processes:

GO term	Partners	Fold	FDR
mitotic spindle organization	5	14.2×	3e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — AML.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	110
Likely benign	15
Benign	5

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
524196	NM_015341.5(NCAPH):c.728C>T (p.Pro243Leu)	Pathogenic
3065922	NM_015341.5(NCAPH):c.19+1G>C	Likely pathogenic
638119	GRCh37/hg19 2q11.1-11.2(chr2:96747466-98193473)x1	Likely pathogenic

SpliceAI

3228 predictions. Top by Δscore:

Variant	Effect	Δscore
2:96335826:A:T	donor_gain	1.0000
2:96335845:CCAGG:C	donor_loss	1.0000
2:96335848:GGTG:G	donor_loss	1.0000
2:96335849:GTGA:G	donor_loss	1.0000
2:96342141:G:GG	donor_gain	1.0000
2:96342750:TTTCA:T	acceptor_loss	1.0000
2:96342751:TTCAG:T	acceptor_loss	1.0000
2:96342752:TCAG:T	acceptor_loss	1.0000
2:96342753:CAGAA:C	acceptor_loss	1.0000
2:96342754:A:AG	acceptor_gain	1.0000
2:96342754:AGAAA:A	acceptor_loss	1.0000
2:96342755:G:GA	acceptor_gain	1.0000
2:96342755:G:T	acceptor_loss	1.0000
2:96342755:GA:G	acceptor_gain	1.0000
2:96342755:GAA:G	acceptor_gain	1.0000
2:96342755:GAAA:G	acceptor_gain	1.0000
2:96342848:AG:A	donor_loss	1.0000
2:96342849:G:GG	donor_gain	1.0000
2:96342849:GT:G	donor_loss	1.0000
2:96342850:T:G	donor_loss	1.0000
2:96342857:G:GT	donor_gain	1.0000
2:96343280:G:GT	donor_gain	1.0000
2:96343283:G:GT	donor_gain	1.0000
2:96344099:TTTTA:T	acceptor_loss	1.0000
2:96344100:TTTA:T	acceptor_loss	1.0000
2:96344101:TTA:T	acceptor_loss	1.0000
2:96344102:TAGAT:T	acceptor_loss	1.0000
2:96344103:A:AG	acceptor_gain	1.0000
2:96344103:AGAT:A	acceptor_gain	1.0000
2:96344104:G:A	acceptor_loss	1.0000

AlphaMissense

4941 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:96342127:T:C	L117P	0.999
2:96342760:T:C	I123T	0.999
2:96342760:T:G	I123S	0.999
2:96342790:T:C	L133S	0.999
2:96343170:C:A	A154D	0.999
2:96343188:C:A	A160D	0.999
2:96343190:A:C	S161R	0.999
2:96343192:C:A	S161R	0.999
2:96343192:C:G	S161R	0.999
2:96343205:G:C	A166P	0.999
2:96342117:T:C	C114R	0.998
2:96343182:T:C	L158P	0.998
2:96343187:G:C	A160P	0.998
2:96342760:T:A	I123N	0.997
2:96342775:C:A	A128D	0.997
2:96342777:T:C	F129L	0.997
2:96342779:T:A	F129L	0.997
2:96342779:T:G	F129L	0.997
2:96343200:T:C	I164T	0.997
2:96343200:T:G	I164S	0.997
2:96343202:T:G	Y165D	0.997
2:96343211:C:A	R168S	0.997
2:96343212:G:C	R168P	0.997
2:96367315:T:C	L647P	0.997
2:96367319:G:C	K648N	0.997
2:96367319:G:T	K648N	0.997
2:96369489:G:C	A719P	0.997
2:96342108:T:G	Y111D	0.996
2:96342784:T:C	L131S	0.996
2:96342790:T:G	L133W	0.996

dbSNP variants (sampled 300 via entrez): RS1000047925 (2:96363062 G>A), RS1000126442 (2:96343066 C>A,G), RS1000146685 (2:96355636 T>C), RS1000191121 (2:96343086 T>C), RS1000191914 (2:96338094 T>A), RS1000333455 (2:96370320 C>T), RS1000343187 (2:96335943 G>A,C), RS1000388139 (2:96376489 A>G), RS1000425084 (2:96349991 A>G), RS1000433820 (2:96355552 C>T), RS1000439125 (2:96376701 G>A), RS1000506256 (2:96369722 T>C), RS1000527026 (2:96357581 C>T), RS1000633484 (2:96351102 G>T), RS1000684286 (2:96351397 G>A)

Disease associations

OMIM: gene MIM:602332 | disease phenotypes: MIM:617985

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly 23, primary, autosomal recessive	Limited	Unknown

Mondo (1): microcephaly 23, primary, autosomal recessive (MONDO:0054806)

Orphanet (0):

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000340	Sloping forehead
HP:0001518	Small for gestational age
HP:0002342	Moderate intellectual disability
HP:0003577	Congenital onset

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006258_46	Diastolic blood pressure	4.000000e-08
GCST90002393_193	Monocyte count	9.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067310 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.74	Kd	180.4	nM	CHEMBL5653589
6.70	ED50	201.7	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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	2148829: Binding affinity to human NCAPH incubated for 45 mins by Kinobead based pull down assay	kd	0.1804	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression, decreases expression	5
sodium arsenite	increases expression, decreases expression	3
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	3
Estradiol	increases expression	3
Valproic Acid	affects expression, decreases expression	3
bisphenol A	decreases expression	2
perfluorooctanoic acid	decreases expression	2
Resveratrol	increases phosphorylation, affects cotreatment, increases expression	2
Acetaminophen	increases expression, decreases expression	2
Clozapine	decreases expression	2
Doxorubicin	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
geraniol	decreases expression	1
tetrahydropalmatine	increases expression	1
beta-lapachone	decreases expression	1
afimoxifene	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
diallyl trisulfide	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
phenethyl isothiocyanate	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
deguelin	increases expression	1
2-palmitoylglycerol	increases 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
CHEMBL5651871	Binding	Binding affinity to human NCAPH 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

Clinical trials (associated diseases)

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