CENPT

Summary

CENPT (centromere protein T, HGNC:25787) is a protein-coding gene on chromosome 16q22.1, encoding Centromere protein T (Q96BT3). Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. It is a selective cancer dependency (DepMap: 86.0% of cell lines).

The centromere is a specialized chromatin domain, present throughout the cell cycle, that acts as a platform on which the transient assembly of the kinetochore occurs during mitosis. All active centromeres are characterized by the presence of long arrays of nucleosomes in which CENPA (MIM 117139) replaces histone H3 (see MIM 601128). CENPT is an additional factor required for centromere assembly (Foltz et al., 2006 [PubMed 16622419]).

Source: NCBI Gene 80152 — RefSeq curated summary.

At a glance

• Gene–disease (curated): short stature and microcephaly with genital anomalies (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 300 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 23
• Cancer dependency (DepMap): dependent in 86.0% of screened cell lines
• MANE Select transcript: NM_025082

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25787
Approved symbol	CENPT
Name	centromere protein T
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13111, CENP-T
Ensembl gene	ENSG00000102901
Ensembl biotype	protein_coding
OMIM	611510
Entrez	80152

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 14 protein_coding, 12 protein_coding_CDS_not_defined, 9 retained_intron, 6 nonsense_mediated_decay

ENST00000436104, ENST00000440851, ENST00000561593, ENST00000562338, ENST00000562462, ENST00000562483, ENST00000562513, ENST00000562787, ENST00000562947, ENST00000563885, ENST00000564128, ENST00000564144, ENST00000564346, ENST00000564538, ENST00000564817, ENST00000565114, ENST00000565132, ENST00000565157, ENST00000565385, ENST00000565436, ENST00000565713, ENST00000566067, ENST00000566758, ENST00000567482, ENST00000567985, ENST00000568069, ENST00000568495, ENST00000568564, ENST00000568652, ENST00000568765, ENST00000569019, ENST00000569094, ENST00000569862, ENST00000574569, ENST00000626059, ENST00000899953, ENST00000937857, ENST00000937858, ENST00000969291, ENST00000969292, ENST00000969293

RefSeq mRNA: 1 — MANE Select: NM_025082 NM_025082

CCDS: CCDS42182

Canonical transcript exons

ENST00000562787 — 16 exons

Exon	Start	End
ENSE00001691564	67833750	67834100
ENSE00002599495	67835172	67835300
ENSE00002624217	67835538	67835658
ENSE00002629419	67847401	67847693
ENSE00003461620	67832455	67832545
ENSE00003472910	67832228	67832315
ENSE00003511041	67831576	67831612
ENSE00003525530	67828667	67828843
ENSE00003540279	67831216	67831358
ENSE00003550008	67828157	67828390
ENSE00003555720	67830390	67830548
ENSE00003563610	67829765	67830088
ENSE00003593560	67832012	67832108
ENSE00003599234	67831754	67831890
ENSE00003660044	67829423	67829516
ENSE00003694282	67828474	67828578

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 98.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.7837 / max 279.5946, expressed in 1812 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157820	21.4600	1808
157822	0.9795	470
157824	0.2504	109
157823	0.0937	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.45	gold quality
cerebellar hemisphere	UBERON:0002245	98.29	gold quality
cerebellar cortex	UBERON:0002129	98.09	gold quality
right testis	UBERON:0004534	97.61	gold quality
left testis	UBERON:0004533	97.53	gold quality
skin of abdomen	UBERON:0001416	97.35	gold quality
skin of leg	UBERON:0001511	97.32	gold quality
granulocyte	CL:0000094	96.22	gold quality
right ovary	UBERON:0002118	96.13	gold quality
left ovary	UBERON:0002119	96.04	gold quality
body of pancreas	UBERON:0001150	96.03	gold quality
lower esophagus mucosa	UBERON:0035834	95.86	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.77	gold quality
sural nerve	UBERON:0015488	95.75	gold quality
endocervix	UBERON:0000458	95.71	gold quality
body of uterus	UBERON:0009853	95.71	gold quality
left uterine tube	UBERON:0001303	95.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.69	gold quality
right frontal lobe	UBERON:0002810	95.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.46	gold quality
lower esophagus	UBERON:0013473	95.45	gold quality
body of stomach	UBERON:0001161	95.42	gold quality
cerebellum	UBERON:0002037	95.41	gold quality
mucosa of stomach	UBERON:0001199	95.27	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.10	gold quality
ectocervix	UBERON:0012249	95.05	gold quality
adenohypophysis	UBERON:0002196	94.95	gold quality
tibial nerve	UBERON:0001323	94.94	gold quality
metanephros cortex	UBERON:0010533	94.92	gold quality
apex of heart	UBERON:0002098	94.83	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting CENPT, 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-4531	99.99	69.70	3181
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-631	97.05	66.93	602

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 86.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 14)

• Study demonstrates that CENP-W forms a DNA-binding complex together with the CCAN component CENP-T; this complex directly associates with nucleosomal DNA and with canonical histone H3, but not with CENP-A, in centromeric regions. (PMID:19070575)
• CENP-T exchange into centromeres is restricted to the S-phase of the cell cycle as revealed by FRAP, suggesting a coreplicational loading mechanism. (PMID:19412974)
• The CENP-T/W complex assembles through a dynamic exchange mechanism in late S-phase and G2, is required for mitosis in each cell cycle and does not persist across cell generations. (PMID:21695110)
• results reveal the molecular function of CENP-T proteins and demonstrate how the Ndc80 complex is anchored to centromeres in a manner that couples chromosome movement to spindle dynamics (PMID:22561346)
• CENP-T provides a structural platform for outer kinetochore assembly. (PMID:23334297)
• CSN5 regulates the stability of the inner kinetochore components CENP-T and CENP-W, providing the first direct link between CSN5 and the mitotic apparatus, highlighting the role of CSN5 as a multifunctional cell cycle regulator. (PMID:23926101)
• CENP-T directly interacts with Ndc80, which in turn promotes KNL1/Mis12 complex recruitment at kinetochores during chromosome segregation. (PMID:25660545)
• We used a synthetic system to dissect how CenH3(CENP-A) contributes to the accumulation of CENP-C and CENP-T, two key components that are necessary for the formation of functional kinetochores (PMID:25843710)
• FACT chaperone stabilizes the soluble CENP-T/-W complex in the cell and promotes dynamics of exchange, enabling CENP-T/-W deposition at centromeres. (PMID:27284163)
• Upon cross-linking, the entire CENPA/CENPB/CENPC/CENPT complex is nuclease-protected over an alpha-satellite dimer that comprises the fundamental unit of centromeric chromatin. We conclude that CENPA/CENPC and CENPT pathways for kinetochore assembly are physically integrated over young alpha-satellite dimers. (PMID:27384170)
• Whereas CENP-C recruits a single MIS12:NDC80 complex, the authors show here that CENP-T binds one MIS12:NDC80 and two NDC80 complexes upon phosphorylation by the mitotic CDK1:Cyclin B complex at three distinct CENP-T sites. (PMID:28012276)
• Levels of centromere aberrations increase upon depletion of CENP-A, CENP-C, and CENP-T/W, during replicative senescence, and in cancer cells. (PMID:28167779)
• report a novel disease gene encoding the constitutive inner kinetochore member CENPT, which is involved in kinetochore targeting and assembly, resulting in severe growth failure in two siblings of a consanguineous family (PMID:29228025)
• these data define a novel molecular mechanism underlying the assembly of CENP-T onto the centromere by a temporally regulated HJURP-CENP-T interaction. (PMID:30459232)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cenpt	ENSDARG00000091271
mus_musculus	Cenpt	ENSMUSG00000036672
rattus_norvegicus	Cenpt	ENSRNOG00000024178

Protein

Protein identifiers

Centromere protein T — Q96BT3 (reviewed: Q96BT3)

Alternative names: Interphase centromere complex protein 22

All UniProt accessions (10): Q96BT3, H3BMP6, H3BN05, H3BQ71, H3BQJ0, H3BQS6, H3BTR4, H3BTS2, H3BUW2, I3L4F8

UniProt curated annotations — full annotation on UniProt →

Function. Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. Part of a nucleosome-associated complex that binds specifically to histone H3-containing nucleosomes at the centromere, as opposed to nucleosomes containing CENPA. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. CENPT has a fundamental role in kinetochore assembly and function. It is one of the inner kinetochore proteins, with most further proteins binding downstream. Required for normal chromosome organization and normal progress through mitosis.

Subunit / interactions. Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex is probably recruited on centromeres by the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. Identified in a centromeric complex containing histones H2A, H2B, H3 and H4, and at least CENPA, CENPB, CENPC, CENPT, CENPN, HJURP, SUPT16H, SSRP1 and RSF1. Interacts (via N-terminus) with the NDC80 complex. Heterodimer with CENPW; this dimer coassembles with CENPS-CENPX heterodimers at centromeres to form the tetrameric CENP-T-W-S-X complex.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore.

Post-translational modifications. Dynamically phosphorylated at Ser-47 and probably also other sites during the cell cycle. Phosphorylated at Ser-47 during G2 phase, metaphase and anaphase, but not during telophase or G1 phase.

Disease relevance. Short stature and microcephaly with genital anomalies (SSMGA) [MIM:618702] An autosomal recessive disease characterized by growth failure resulting in severe short stature, severe microcephaly, and delayed and dissociated bone age. Additional features include global psychomotor developmental delay, pubertal delay and genital anomalies. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The largest part of the sequence forms an elongated and flexible stalk structure that is connected to a C-terminal globular domain with a histone-type fold.

Similarity. Belongs to the CENP-T/CNN1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96BT3-1	1	yes
Q96BT3-2	2
Q96BT3-3	3

RefSeq proteins (1): NP_079358* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009072	Histone-fold	Homologous_superfamily
IPR028255	CENP-T	Family
IPR032373	CENP-T_N	Domain
IPR035425	CENP-T/H4_C	Domain

Pfam: PF15511, PF16171

UniProt features (33 total): modified residue 9, helix 5, compositionally biased region 5, region of interest 4, splice variant 4, strand 3, chain 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
28OP	ELECTRON MICROSCOPY	2.7
7R5S	ELECTRON MICROSCOPY	2.83
7XHO	ELECTRON MICROSCOPY	3.29
9TAW	ELECTRON MICROSCOPY	3.54
7XHN	ELECTRON MICROSCOPY	3.71
9TAX	ELECTRON MICROSCOPY	4.5
7QOO	ELECTRON MICROSCOPY	4.6
7YWX	ELECTRON MICROSCOPY	12
9TAY	ELECTRON MICROSCOPY	15.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96BT3-F1	57.20	0.12

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 (9): 47, 85, 343, 345, 356, 373, 385, 386, 397

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-606279	Deposition of new CENPA-containing nucleosomes at the centromere
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69618	Mitotic Spindle Checkpoint
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-73886	Chromosome Maintenance
R-HSA-774815	Nucleosome assembly
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 203 (showing top): GOBP_CHROMOSOME_ORGANIZATION, chr16q22, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MODULE_493, RICKMAN_METASTASIS_DN, GOBP_ORGANELLE_ASSEMBLY, GOBP_MITOTIC_CELL_CYCLE, MODULE_277, XU_GH1_EXOGENOUS_TARGETS_UP, GOBP_KINETOCHORE_ORGANIZATION, REACTOME_CELL_CYCLE_CHECKPOINTS, GOCC_CHROMOSOMAL_REGION, GOCC_NUCLEAR_BODY, GOBP_CELL_DIVISION

GO Biological Process (5): mitotic cell cycle (GO:0000278), chromosome segregation (GO:0007059), chromosome organization (GO:0051276), cell division (GO:0051301), kinetochore assembly (GO:0051382)

GO Molecular Function (3): DNA binding (GO:0003677), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (8): chromosome, centromeric region (GO:0000775), kinetochore (GO:0000776), inner kinetochore (GO:0000939), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear body (GO:0016604), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cell Cycle	3
Mitotic Prometaphase	2
M Phase	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Nucleosome assembly	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle Checkpoints	1
Chromosome Maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	3
cellular anatomical structure	2
cell cycle	1
mitotic nuclear division	1
cell cycle process	1
organelle organization	1
cellular process	1
kinetochore organization	1
protein-containing complex assembly	1
membraneless organelle assembly	1
nucleic acid binding	1
protein dimerization activity	1
binding	1
chromosomal region	1
condensed chromosome, centromeric region	1
supramolecular complex	1
kinetochore	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
nucleoplasm	1

Protein interactions and networks

STRING

918 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CENPT	CENPW	Q5EE01	997
CENPT	CENPN	Q96H22	995
CENPT	CENPC	Q03188	993
CENPT	CENPU	Q71F23	991
CENPT	CENPS	Q8N2Z9	989
CENPT	CENPH	Q9H3R5	986
CENPT	CENPX	A8MT69	981
CENPT	CENPM	Q9NSP4	966
CENPT	CENPO	Q9BU64	966
CENPT	CENPI	Q92674	952
CENPT	CENPP	Q6IPU0	948
CENPT	CENPA	P49450	940
CENPT	CENPQ	Q7L2Z9	937
CENPT	CENPL	Q8N0S6	930
CENPT	SPC24	Q8NBT2	930

IntAct

35 interactions, top by confidence:

A	B	Type	Score
CENPS	CENPX	psi-mi:“MI:0915”(physical association)	0.810
CENPW	CENPT	psi-mi:“MI:0915”(physical association)	0.780
CENPW	CENPT	psi-mi:“MI:0407”(direct interaction)	0.780
ITGB3BP	CENPU	psi-mi:“MI:0914”(association)	0.710
ATXN7L3	USP27X	psi-mi:“MI:0914”(association)	0.640
CENPH	PSMD11	psi-mi:“MI:0914”(association)	0.530
CENPT	SPC24	psi-mi:“MI:0915”(physical association)	0.520
Cenph	CENPX	psi-mi:“MI:0914”(association)	0.350
CENPO	CENPX	psi-mi:“MI:0914”(association)	0.350
CENPQ	CENPX	psi-mi:“MI:0914”(association)	0.350
ITGB3BP	ATP5MF-PTCD1	psi-mi:“MI:0914”(association)	0.350
CENPU	CENPX	psi-mi:“MI:0914”(association)	0.350
CAV3	SHTN1	psi-mi:“MI:0914”(association)	0.350
CENPT	CENPA	psi-mi:“MI:0914”(association)	0.350
RPL36	GTPBP10	psi-mi:“MI:0914”(association)	0.350
RPL28	GTPBP10	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
SRSF5	FBLL1	psi-mi:“MI:0914”(association)	0.350
ZBTB47	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
CENPW	PMVK	psi-mi:“MI:0914”(association)	0.350
H2BC10	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
SMC5	DKFZp686H10254	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (57): CENPT (Proximity Label-MS), CENPT (Affinity Capture-MS), CENPT (Affinity Capture-MS), CENPT (Affinity Capture-MS), CENPT (Affinity Capture-MS), CENPT (Affinity Capture-MS), CENPT (Affinity Capture-MS), CENPT (Affinity Capture-MS), CENPT (Affinity Capture-Western), CENPT (Affinity Capture-RNA), CENPT (FRET), CENPW (FRET), CENPT (Affinity Capture-RNA), DHX29 (Two-hybrid), CENPT (Two-hybrid)

ESM2 similar proteins: A0A1L8H8C0, A0A1L8HFX9, A0JM08, A2AHC3, A5WUN7, B1H1S4, B2GUZ2, D3Z8E6, E9PVX6, E9Q309, F1MCY2, F1NPG5, F1R983, P49452, P50534, P62025, Q0P5H2, Q2PFD7, Q3T8J9, Q3TJM4, Q498L0, Q4R5U8, Q535K8, Q561R1, Q58EL7, Q5HZA1, Q5QJE6, Q5SW79, Q5T5Y3, Q5U3U6, Q5VT06, Q5XHF3, Q6A065, Q6DJL7, Q6IRN6, Q6P6I6, Q71M44, Q7TSH4, Q80YR7, Q8AV28

Diamond homologs: F1NPG5, Q3TJM4, Q4R5U8, Q561R1, Q96BT3, Q9HGK9, P02309, P04915, P08436, P09322, P0CG89, P27996, P35057, P35059, P40287, P50566, P59259, P62776, P62777, P62778, P62779, P62780, P62781, P62782, P62783, P62784, P62785, P62786, P62787, P62788, P62794, P62795, P62796, P62797, P62798, P62799, P62800, P62801, P62802, P62803

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CENPT	“form complex”	“CCAN complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 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
Nucleosome assembly	9	171.3×	7e-17
Chromosome Maintenance	9	76.1×	9e-14
Deposition of new CENPA-containing nucleosomes at the centromere	10	63.4×	2e-14
Amplification of signal from the kinetochores	8	63.0×	2e-11
Mitotic Spindle Checkpoint	8	50.8×	8e-11
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	8	37.3×	9e-10
Mitotic Metaphase and Anaphase	8	31.0×	3e-09
Mitotic Anaphase	8	31.0×	3e-09

GO biological processes:

GO term	Partners	Fold	FDR
chromosome segregation	10	54.3×	3e-13
cell division	6	8.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	172
Likely benign	84
Benign	22

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
800555	NM_025082.4(CENPT):c.1186+1G>A	Pathogenic
393304	NM_020457.3(THAP11):c.240C>G (p.Phe80Leu)	Likely pathogenic

SpliceAI

3841 predictions. Top by Δscore:

Variant	Effect	Δscore
16:67828469:CTCA:C	donor_loss	1.0000
16:67828470:TCAC:T	donor_loss	1.0000
16:67828471:CA:C	donor_loss	1.0000
16:67828472:A:AC	donor_gain	1.0000
16:67828473:C:CC	donor_gain	1.0000
16:67828473:CCG:C	donor_gain	1.0000
16:67828579:C:CC	acceptor_gain	1.0000
16:67828666:CCA:C	donor_gain	1.0000
16:67829421:A:AC	donor_gain	1.0000
16:67829422:C:CC	donor_gain	1.0000
16:67829422:CA:C	donor_gain	1.0000
16:67829422:CACTG:C	donor_gain	1.0000
16:67829425:TGCAG:T	donor_gain	1.0000
16:67829513:CTTG:C	acceptor_gain	1.0000
16:67829517:C:CC	acceptor_gain	1.0000
16:67830388:A:AC	donor_gain	1.0000
16:67830389:C:CC	donor_gain	1.0000
16:67830389:CTATT:C	donor_gain	1.0000
16:67830426:TGCG:T	donor_gain	1.0000
16:67831214:A:AC	donor_gain	1.0000
16:67831215:C:CC	donor_gain	1.0000
16:67828461:T:A	donor_gain	0.9900
16:67828472:ACCG:A	donor_gain	0.9900
16:67828473:CCGC:C	donor_gain	0.9900
16:67828574:CTAGG:C	acceptor_gain	0.9900
16:67828575:TAGG:T	acceptor_gain	0.9900
16:67828577:GG:G	acceptor_gain	0.9900
16:67828578:GC:G	acceptor_loss	0.9900
16:67828579:C:CG	acceptor_loss	0.9900
16:67828583:C:CT	acceptor_gain	0.9900

AlphaMissense

3585 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:67828337:A:G	L539P	0.986
16:67828516:C:G	R507P	0.984
16:67828477:C:G	R520P	0.983
16:67828543:A:G	L498P	0.982
16:67828322:C:G	R544P	0.980
16:67828496:C:G	D514H	0.979
16:67828313:A:G	L547P	0.978
16:67828474:C:G	R521P	0.977
16:67828495:T:C	D514G	0.977
16:67828483:A:G	L518P	0.975
16:67828533:A:C	F501L	0.975
16:67828533:A:T	F501L	0.975
16:67828535:A:G	F501L	0.975
16:67828495:T:G	D514A	0.974
16:67828555:A:G	L494P	0.974
16:67828486:A:G	L517P	0.972
16:67828492:A:G	L515P	0.971
16:67828523:C:G	A505P	0.968
16:67828382:A:G	L524P	0.967
16:67831791:A:C	F162L	0.964
16:67831791:A:T	F162L	0.964
16:67831793:A:G	F162L	0.964
16:67828352:A:G	L534P	0.960
16:67828495:T:A	D514V	0.960
16:67828313:A:T	L547H	0.959
16:67828517:G:T	R507S	0.959
16:67828379:A:T	V525D	0.958
16:67828534:A:G	F501S	0.958
16:67831792:A:G	F162S	0.956
16:67828310:A:G	I548T	0.955

dbSNP variants (sampled 300 via entrez): RS1000082581 (16:67845853 C>T), RS1000285688 (16:67838648 C>A,T), RS1000407899 (16:67833361 G>C), RS1000486335 (16:67833058 C>T), RS1000657579 (16:67838850 T>C), RS1000832563 (16:67848251 C>T), RS1000978795 (16:67842871 A>C,G), RS1001001176 (16:67828183 TG>T,TGG), RS1001019773 (16:67842406 G>A), RS1001031659 (16:67837203 C>T), RS1001342422 (16:67848656 C>T), RS1001477496 (16:67833992 C>G,T), RS1001534668 (16:67833823 G>A,C), RS1001814762 (16:67848311 G>A,T), RS1001837214 (16:67832697 C>A,T)

Disease associations

OMIM: gene MIM:611510 | disease phenotypes: MIM:618702, MIM:620947, MIM:309541, MIM:620940

GenCC curated gene-disease

Disease	Classification	Inheritance
short stature and microcephaly with genital anomalies	Limited	Autosomal recessive

Mondo (4): short stature and microcephaly with genital anomalies (MONDO:0032875), spinocerebellar ataxia 51 (MONDO:0975800), methylmalonic acidemia with homocystinuria, type cblX (MONDO:0010657), methylmalonic aciduria and homocystinuria, cb1L type (MONDO:0975798)

Orphanet (1): Methylmalonic acidemia with homocystinuria, type cblX (Orphanet:369962)

HPO phenotypes

23 total (23 of 23 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000054	Micropenis
HP:0000160	Narrow mouth
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000444	Convex nasal ridge
HP:0000448	Prominent nose
HP:0000494	Downslanted palpebral fissures
HP:0000540	Hypermetropia
HP:0000823	Delayed puberty
HP:0001263	Global developmental delay
HP:0001508	Failure to thrive
HP:0001741	Phimosis
HP:0001804	Hypoplastic fingernail
HP:0002020	Gastroesophageal reflux
HP:0002650	Scoliosis
HP:0002857	Genu valgum
HP:0003241	External genital hypoplasia
HP:0003510	Severe short stature
HP:0004325	Decreased body weight
HP:0005832	Dysharmonic delayed bone age
HP:0011968	Feeding difficulties
HP:0025515	Delayed thelarche

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002539_84	Schizophrenia	2.000000e-08
GCST006803_42	Schizophrenia	4.000000e-08
GCST010002_113	Refractive error	2.000000e-14

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563136	Mental Retardation, X-Linked 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	increases sumoylation	1
bufotalin	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
beta-lapachone	decreases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
ICG 001	decreases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	decreases expression, affects cotreatment	1
Diethylhexyl Phthalate	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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