THAP11

Summary

THAP11 (THAP domain containing 11, HGNC:23194) is a protein-coding gene on chromosome 16q22.1, encoding THAP domain-containing protein 11 (Q96EK4). Transcription factor, which has both transcriptional activation and repression activities. It is a selective cancer dependency (DepMap: 56.3% of cell lines).

The protein encoded by this gene contains a THAP domain, which is a conserved DNA-binding domain that has striking similarity to the site-specific DNA-binding domain (DBD) of Drosophila P element transposases.

Source: NCBI Gene 57215 — RefSeq curated summary.

At a glance

• Gene–disease (curated): methylmalonic aciduria and homocystinuria (Limited, ClinGen) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 8 total — 1 pathogenic
• Phenotypes (HPO): 15
• Cancer dependency (DepMap): dependent in 56.3% of screened cell lines
• MANE Select transcript: NM_020457

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23194
Approved symbol	THAP11
Name	THAP domain containing 11
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	HRIHFB2206, CTG-B45d, CTG-B43a, RONIN
Ensembl gene	ENSG00000168286
Ensembl biotype	protein_coding
OMIM	609119
Entrez	57215

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000303596

RefSeq mRNA: 1 — MANE Select: NM_020457 NM_020457

CCDS: CCDS10847

Canonical transcript exons

ENST00000303596 — 1 exons

Exon	Start	End
ENSE00001173220	67842320	67844195

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 94.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.9187 / max 92.7944, expressed in 1796 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154680	17.5011	1795
207920	1.4176	872

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	94.31	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.12	gold quality
tendon of biceps brachii	UBERON:0008188	92.99	gold quality
granulocyte	CL:0000094	92.98	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.87	gold quality
vastus lateralis	UBERON:0001379	92.14	gold quality
gastrocnemius	UBERON:0001388	92.09	gold quality
quadriceps femoris	UBERON:0001377	91.56	gold quality
muscle of leg	UBERON:0001383	91.55	gold quality
nipple	UBERON:0002030	91.55	gold quality
muscle organ	UBERON:0001630	91.44	gold quality
apex of heart	UBERON:0002098	91.34	gold quality
medial globus pallidus	UBERON:0002477	91.22	gold quality
saphenous vein	UBERON:0007318	91.06	gold quality
skeletal muscle tissue	UBERON:0001134	90.64	gold quality
right coronary artery	UBERON:0001625	89.85	gold quality
leukocyte	CL:0000738	89.78	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.75	gold quality
biceps brachii	UBERON:0001507	89.66	gold quality
lower esophagus	UBERON:0013473	89.61	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.61	gold quality
descending thoracic aorta	UBERON:0002345	89.57	gold quality
monocyte	CL:0000576	89.55	gold quality
mononuclear cell	CL:0000842	89.47	gold quality
left uterine tube	UBERON:0001303	89.46	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.45	gold quality
heart left ventricle	UBERON:0002084	89.39	gold quality
muscle tissue	UBERON:0002385	89.39	gold quality
globus pallidus	UBERON:0001875	89.35	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.95
E-MTAB-4850	no	204.86

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
CCND1	Activation
CDKN1A
HCFC1
JAK2
MYC	Repression
ODC1

JASPAR motifs

Motif	Name	Family
MA1573.1	THAP11	THAP-related factors

JASPAR matrix evidence (PMIDs): PMID:20581084

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

65 targeting THAP11, 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-8485	100.00	77.57	4731
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3605-5P	99.96	67.12	932
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-766-5P	99.47	67.91	2225

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 56.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 18)

• Results suggest that THAP11 functions as a cell growth suppressor by negatively regulating the expression of c-Myc. (PMID:19008924)
• the induced THAP11 might be one of transcriptional regulators of c-Myc expression in CML cell. (PMID:21400515)
• identify THAP11 as a transcriptional regulator differentially expressed in human colon cancer (PMID:22371484)
• In HCC patients, the expression of THAP11 mRNA significantly correlated with PCBP1 mRNA expression. Our results suggest a novel role of THAP11 in CD44 alternative splicing and hepatoma invasion (PMID:22673507)
• HCFC1 is a common component of active human CpG-island promoters and coincides with ZNF143, THAP11, YY1, and GABP transcription factor occupancy. (PMID:23539139)
• that THAP11 reversibly regulated erythroid and megakaryocytic differentiation. (PMID:24637716)
• THAP11, ZNF143, and HCF-1 form a mutually dependent complex on chromatin, which is independent of E2F occupancy. (PMID:25437553)
• the crystal structure of the C-ter region of THAP11 forms a left-handed parallel homo-dimeric coiled-coil structure possessing several unusual features. (PMID:26975212)
• The M4 motif (ACTAYRNNNCCCR) is a functional regulatory bipartite cis-element, which engages a THAP11/HCF-1 complex via binding to the ACTAYR module, while the CCCRRNRNRC subsequence part constitutes a binding platform for Ikaros and NFKB1 (PMID:27576892)
• We sequenced THAP11 by Sanger sequencing and discovered a potentially pathogenic, homozygous variant in THAP11, c.240C > G (p.Phe80Leu). Further, we provide functional data in model organisms that suggests that both HCFC1 and THAP11 are essential for normal brain development and neural precursor differentiation. (PMID:28449119)
• A transcriptional repressor network including THAP domain containing 11 protein (THAP11) was identified and negatively regulates endogenous PARKIN abundance. (PMID:29269392)
• THAP11F80L exhibited a strong effect on association with the MMACHC promoter and led to a decrease in MMACHC gene transcription, suggesting that the THAP11F80L mutation is directly responsible for the observed cobalamin disorder (PMID:31905202)
• THAP11 inhibited growth of esophageal cancer cells (PMID:31969497)
• THAP11 Functions as a Tumor Suppressor in Gastric Cancer through Regulating c-Myc Signaling Pathways. (PMID:32908912)
• CAG Repeat Expansion in THAP11 Is Associated with a Novel Spinocerebellar Ataxia. (PMID:37148549)
• Exploring THAP11 Repeat Expansion beyond Chinese-Ancestry Cohorts: An Examination of 1000 Genomes and UK Biobank Data. (PMID:38113319)
• CircNRD1 elevates THAP domain containing 11 through sequestering microRNA-421 to inhibit gastric cancer growth and tumorigenesis. (PMID:38602237)
• THAP11 CAG Repeat Expansion Is Rare or Absent in the Taiwanese Cohort with Cerebellar Ataxia. (PMID:38757579)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	thap11	ENSDARG00000036055
mus_musculus	Thap11	ENSMUSG00000036442
rattus_norvegicus	Thap11	ENSRNOG00000019109

Protein

Protein identifiers

THAP domain-containing protein 11 — Q96EK4 (reviewed: Q96EK4)

All UniProt accessions (1): Q96EK4

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor, which has both transcriptional activation and repression activities. Also modulates chromatin accessibility. In complex with HCFC1 and ZNF143, regulates the expression of several genes, including AP2S1, ESCO2, OPHN1, RBL1, UBXN8 and ZNF32. May regulate the expression of genes that encode both cytoplasmic and mitochondrial ribosomal proteins. Required for normal mitochondrial development and function. Regulates mitochondrial gene expression, including that of components of the electron transport chain. Involved in the maintainance of pluripotency in early embryonic cells, possibly through its action on mitochondrial maturation which is required to meet high energy demands of these cells. Required for early development of retina, preventing premature exit of retinal progenitor cells from the cell cycle. This effect may also be mediated by its action on mitochondria. Through the regulation of MMACHC gene expression, controls cobalamin metabolism. Required for normal brain development and neural precursor differentiation. Involved in cell growth.

Subunit / interactions. Forms homodimers. Interacts via HBM with HCFC1. Forms a complex with HCFC1 and ZNF143.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in skin fibroblasts.

Disease relevance. Methylmalonic aciduria and homocystinuria type cblL (MAHCL) [MIM:620940] An autosomal recessive disorder of cobalamin metabolism clinically characterized by early-onset seizures, and profound global developmental delay with severe intellectual disability. Metabolic features are mild methylmalonic aciduria, low-normal plasma methionine, and high-normal plasma homocysteine. The disease is caused by variants affecting the gene represented in this entry. Spinocerebellar ataxia 51 (SCA51) [MIM:620947] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA51 is an autosomal dominant form with age-dependent penetrance and genetic anticipation. The disease is caused by variants affecting the gene represented in this entry. SCA51 is caused by CAG(n) trinucleotide repeat expansions. The expansion associated with ataxia phenotype is over 45 repeats. There is a correlation between the size of the CAG(n) repeat and symptom onset. A patient with onset at 4 years of age showed 100 repeats, whereas patients with 45 to 55 repeats had a disease onset in adulthood. CAG(n) repeat expansion leads to THAP11 protein aggregation in the cytoplasm and decreased cell viability.

Polymorphism. The length of the poly-Gln region is variable in the population, ranging from about 20 to 38 repeats.

Similarity. Belongs to the THAP11 family.

RefSeq proteins (1): NP_065190* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006612	THAP_Znf	Domain

Pfam: PF05485

UniProt features (14 total): helix 3, strand 3, chain 1, zinc finger region 1, region of interest 1, coiled-coil region 1, short sequence motif 1, compositionally biased region 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5AJS	X-RAY DIFFRACTION	2.3
2LAU	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EK4-F1	69.57	0.27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 203 (showing top): GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, chr16q22, SP3_Q3, GOBP_NEUROGENESIS, BROWNE_HCMV_INFECTION_16HR_UP, CACCAGC_MIR138, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, MCAATNNNNNGCG_UNKNOWN, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, RGTTAMWNATT_HNF1_01, TGCTGAY_UNKNOWN, GOBP_ELECTRON_TRANSPORT_CHAIN

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), cell population proliferation (GO:0008283), electron transport chain (GO:0022900), neuron differentiation (GO:0030182), negative regulation of neuron apoptotic process (GO:0043524), regulation of mitochondrial transcription (GO:1903108), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (10): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), core promoter sequence-specific DNA binding (GO:0001046), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), zinc ion binding (GO:0008270), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): chromatin (GO:0000785), nucleoplasm (GO:0005654), cytosol (GO:0005829), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
cellular anatomical structure	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
negative regulation of DNA-templated transcription	1
cellular process	1
generation of precursor metabolites and energy	1
cell differentiation	1
generation of neurons	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
mitochondrial transcription	1
regulation of mitochondrial gene expression	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription repressor activity	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
chromosome	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

462 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THAP11	THAP7	Q9BT49	938
THAP11	THAP1	Q9NVV9	905
THAP11	THAP4	Q8WY91	905
THAP11	THAP12	O43422	899
THAP11	THAP2	Q9H0W7	890
THAP11	THAP3	Q8WTV1	877
THAP11	ZNF143	P52747	823
THAP11	HCFC1	P51610	803
THAP11	THAP5	Q7Z6K1	652
THAP11	THAP8	Q8NA92	581
THAP11	THAP10	Q9P2Z0	570
THAP11	POU5F1	P31359	562
THAP11	THAP9	Q9H5L6	546
THAP11	MMACHC	Q9Y4U1	524
THAP11	MCRS1	Q96EZ8	484

IntAct

155 interactions, top by confidence:

A	B	Type	Score
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
THAP11	CTBP1	psi-mi:“MI:0915”(physical association)	0.720
CTBP1	THAP11	psi-mi:“MI:0915”(physical association)	0.720
THAP11	PSMC5	psi-mi:“MI:0915”(physical association)	0.660
CAMKK2	OBSL1	psi-mi:“MI:0914”(association)	0.640
THAP11	HCFC1	psi-mi:“MI:0915”(physical association)	0.630
HCFC1	THAP11	psi-mi:“MI:0915”(physical association)	0.630
THAP11	HCFC1	psi-mi:“MI:0914”(association)	0.630
YWHAE	RGS12	psi-mi:“MI:0914”(association)	0.610
THAP11	VPS52	psi-mi:“MI:0915”(physical association)	0.560
VPS52	THAP11	psi-mi:“MI:0915”(physical association)	0.560
YWHAE	SRSF10	psi-mi:“MI:0914”(association)	0.560
PCBP1	THAP11	psi-mi:“MI:0915”(physical association)	0.560
PCBP1	THAP11	psi-mi:“MI:0403”(colocalization)	0.560
Casp3	THAP11	psi-mi:“MI:0915”(physical association)	0.530
THAP11	Casp3	psi-mi:“MI:0570”(protein cleavage)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
IL20RA	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
THAP11	OGT	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
THAP3	CASC3	psi-mi:“MI:0914”(association)	0.530
TSPAN5	SC5D	psi-mi:“MI:0914”(association)	0.530
ABRAXAS2	LAMC1	psi-mi:“MI:0914”(association)	0.530

BioGRID (172): C9orf16 (Two-hybrid), LRRC45 (Two-hybrid), PFDN6 (Two-hybrid), PSMC5 (Two-hybrid), THAP11 (Two-hybrid), THAP11 (Affinity Capture-MS), THAP11 (Affinity Capture-MS), THAP11 (Affinity Capture-MS), THAP11 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), OGT (Affinity Capture-MS), HCFC1 (Affinity Capture-MS), THAP11 (Affinity Capture-MS), THAP11 (Affinity Capture-MS), THAP11 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5NVS8, A1L2U9, A2A891, A4IGQ8, A5PKF5, B1WAZ8, B5XCB8, E1BKK0, F1LMN3, O94972, P23804, P56950, P86174, Q0IH98, Q12766, Q14B70, Q58FA4, Q5NVM3, Q5RET9, Q5T7W0, Q5ZHN5, Q69ZF8, Q6A098, Q6IQ49, Q6IR68, Q6PCX9, Q6TGZ4, Q6YND2, Q6ZU67, Q7YRZ8, Q7Z7J5, Q7ZVU1, Q80YY7, Q8C0R0, Q8C4P0, Q8CII0, Q8K0L9, Q8N680, Q8N8K9, Q93073

Diamond homologs: A4IGQ8, A5PKF5, Q6IR68, Q6TGZ4, Q96EK4, Q9JJD0, Q9VGA4, O43422

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	2
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3340129	THAP11, (CAG)n REPEAT EXPANSION	Pathogenic

SpliceAI

341 predictions. Top by Δscore:

Variant	Effect	Δscore
16:67843484:G:GT	donor_gain	0.9900
16:67843492:G:GT	donor_gain	0.9900
16:67843493:A:T	donor_gain	0.9900
16:67843499:AACTG:A	donor_gain	0.9800
16:67843191:GCTGC:G	donor_gain	0.9600
16:67843129:TGC:T	donor_gain	0.9000
16:67843368:G:GT	donor_gain	0.8900
16:67843209:G:GT	donor_gain	0.8700
16:67843131:C:T	donor_gain	0.8600
16:67843607:GCT:G	donor_gain	0.8500
16:67843135:TG:T	donor_gain	0.8300
16:67843136:GG:G	donor_gain	0.8300
16:67843179:TCG:T	donor_gain	0.8300
16:67843452:G:GT	donor_gain	0.8100
16:67843185:T:G	donor_gain	0.7800
16:67843448:G:GT	donor_gain	0.7800
16:67843449:A:T	donor_gain	0.7500
16:67842622:TCTAC:T	donor_gain	0.7300
16:67842639:GACGC:G	donor_gain	0.7300
16:67843205:G:T	donor_gain	0.7300
16:67843365:ATGG:A	acceptor_gain	0.7300
16:67843495:T:G	donor_gain	0.7300
16:67843498:GAACT:G	donor_gain	0.7300
16:67843479:C:CT	acceptor_gain	0.7200
16:67843136:G:GT	donor_gain	0.6900
16:67843204:G:GT	donor_gain	0.6900
16:67843212:GCTGC:G	donor_gain	0.6900
16:67843213:CTGCC:C	donor_gain	0.6900
16:67843481:C:T	donor_gain	0.6900
16:67842597:TCG:T	donor_gain	0.6700

AlphaMissense

2027 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:67842564:T:C	F4L	1.000
16:67842566:T:A	F4L	1.000
16:67842566:T:G	F4L	1.000
16:67842570:T:A	C6S	1.000
16:67842570:T:C	C6R	1.000
16:67842571:G:A	C6Y	1.000
16:67842571:G:C	C6S	1.000
16:67842571:G:T	C6F	1.000
16:67842572:C:G	C6W	1.000
16:67842573:T:C	C7R	1.000
16:67842574:G:A	C7Y	1.000
16:67842585:T:A	C11S	1.000
16:67842585:T:C	C11R	1.000
16:67842586:G:A	C11Y	1.000
16:67842586:G:C	C11S	1.000
16:67842587:C:G	C11W	1.000
16:67842621:T:A	F23I	1.000
16:67842621:T:C	F23L	1.000
16:67842622:T:C	F23S	1.000
16:67842622:T:G	F23C	1.000
16:67842623:C:A	F23L	1.000
16:67842623:C:G	F23L	1.000
16:67842624:T:G	Y24D	1.000
16:67842631:T:C	F26S	1.000
16:67842631:T:G	F26C	1.000
16:67842634:C:A	P27Q	1.000
16:67842634:C:T	P27L	1.000
16:67842660:T:A	W36R	1.000
16:67842660:T:C	W36R	1.000
16:67842661:G:C	W36S	1.000

dbSNP variants (sampled 300 via entrez): RS1000978795 (16:67842871 A>C,G), RS1001019773 (16:67842406 G>A), RS1002196565 (16:67843147 C>T), RS1002994345 (16:67840621 G>A,T), RS1003022008 (16:67840405 G>A), RS1003204515 (16:67844671 T>G), RS1003235295 (16:67844387 C>T), RS1004130867 (16:67843914 C>T), RS1004163776 (16:67843627 C>A,G,T), RS1004580138 (16:67842152 G>A,T), RS1005058504 (16:67842054 G>A,C), RS1005802281 (16:67842466 G>C,T), RS1006139148 (16:67841372 T>C), RS1006170460 (16:67841028 T>C), RS1007030638 (16:67842040 T>C)

Disease associations

OMIM: gene MIM:609119 | disease phenotypes: MIM:620947

GenCC curated gene-disease

Disease	Classification	Inheritance
methylmalonic aciduria and homocystinuria	Limited	Autosomal recessive
inborn disorder of cobalamin metabolism and transport	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
methylmalonic aciduria and homocystinuria	Limited	AR

Mondo (3): spinocerebellar ataxia 51 (MONDO:0975800), methylmalonic aciduria and homocystinuria (MONDO:0016826), inborn disorder of cobalamin metabolism and transport (MONDO:0019220)

Orphanet (0):

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000508	Ptosis
HP:0000514	Slow saccadic eye movements
HP:0000639	Nystagmus
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001336	Myoclonus
HP:0002015	Dysphagia
HP:0002066	Gait ataxia
HP:0003474	Somatic sensory dysfunction
HP:0003596	Middle age onset
HP:0007256	Abnormal pyramidal sign
HP:0011463	Childhood onset
HP:0025710	Late young adult onset
HP:0100543	Cognitive impairment

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002539_84	Schizophrenia	2.000000e-08
GCST004601_139	Red blood cell count	1.000000e-15
GCST006803_42	Schizophrenia	4.000000e-08
GCST90002397_245	Mean spheric corpuscular volume	1.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537359	Methylmalonic acidemia with homocystinuria (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	increases sumoylation	1
glycidyl methacrylate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Ethanol	affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Indomethacin	decreases expression, affects cotreatment	1
Methotrexate	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Polycyclic Aromatic Hydrocarbons	increases abundance, affects cotreatment, decreases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A7L1	SEES3-1V human THAP11, clone1	Embryonic stem cell	Male
CVCL_A7L2	SEES3-1V human THAP11, clone2	Embryonic stem cell	Male
CVCL_A7L3	SEES3-1V human THAP11, clone3	Embryonic stem cell	Male
CVCL_B5E1	HEK293 THAP11F80L #8	Transformed cell line	Female
CVCL_B5E2	HEK293 THAP11HBM #1	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02679833	Not specified	COMPLETED	Effect of Toothpaste Fortified With Cyanocobalamin on Vitamin B12 Status
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening