ZBTB38

Summary

ZBTB38 (zinc finger and BTB domain containing 38, HGNC:26636) is a protein-coding gene on chromosome 3q23, encoding Zinc finger and BTB domain-containing protein 38 (Q8NAP3). Transcriptional regulator with bimodal DNA-binding specificity.

The protein encoded by this gene is a zinc finger transcriptional activator that binds methylated DNA. The encoded protein can form homodimers or heterodimers through the zinc finger domains. In mouse, inhibition of this protein has been associated with apoptosis in some cell types.

Source: NCBI Gene 253461 — RefSeq curated summary.

At a glance

• GWAS associations: 136
• Clinical variants (ClinVar): 128 total
• MANE Select transcript: NM_001376113

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26636
Approved symbol	ZBTB38
Name	zinc finger and BTB domain containing 38
Location	3q23
Locus type	gene with protein product
Status	Approved
Aliases	FLJ35036, CIBZ, ZNF921, PPP1R171
Ensembl gene	ENSG00000177311
Ensembl biotype	protein_coding
OMIM	612218
Entrez	253461

Gene structure

Transcript identifiers

Ensembl transcripts: 57 — 49 protein_coding, 6 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000321464, ENST00000441582, ENST00000503809, ENST00000504673, ENST00000506623, ENST00000507657, ENST00000507722, ENST00000509813, ENST00000509842, ENST00000509883, ENST00000510338, ENST00000510726, ENST00000512276, ENST00000512327, ENST00000512769, ENST00000513249, ENST00000513258, ENST00000513570, ENST00000513619, ENST00000514251, ENST00000636289, ENST00000637056, ENST00000637706, ENST00000860260, ENST00000860261, ENST00000860262, ENST00000860263, ENST00000860264, ENST00000860265, ENST00000860266, ENST00000860267, ENST00000860268, ENST00000860269, ENST00000860270, ENST00000860271, ENST00000860272, ENST00000860273, ENST00000860274, ENST00000860275, ENST00000860276, ENST00000860277, ENST00000860278, ENST00000860279, ENST00000860280, ENST00000860281, ENST00000860282, ENST00000928306, ENST00000961278, ENST00000961279, ENST00000961280, ENST00000961281, ENST00000961282, ENST00000961283, ENST00000961284, ENST00000961285, ENST00000961286, ENST00000961287

RefSeq mRNA: 85 — MANE Select: NM_001376113 NM_001080412, NM_001350099, NM_001350100, NM_001376112, NM_001376113, NM_001376114, NM_001376115, NM_001376116, NM_001376117, NM_001376118, NM_001376119, NM_001376120, NM_001376121, NM_001376122, NM_001376123, NM_001376124, NM_001376125, NM_001376126, NM_001376127, NM_001376128, NM_001376142, NM_001376143, NM_001376150, NM_001376152, NM_001376157, NM_001376158, NM_001376159, NM_001376160, NM_001376161, NM_001376162, NM_001376163, NM_001376164, NM_001376165, NM_001376166, NM_001376167, NM_001376168, NM_001376169, NM_001376170, NM_001376171, NM_001376172, NM_001376173, NM_001376174, NM_001376175, NM_001376176, NM_001376177, NM_001376178, NM_001376179, NM_001376180, NM_001376181, NM_001376182, NM_001376183, NM_001376184, NM_001376185, NM_001376186, NM_001376187, NM_001376188, NM_001376189, NM_001376190, NM_001387941, NM_001387945, NM_001387947, NM_001387948, NM_001387950, NM_001387952, NM_001387953, NM_001387957, NM_001387959, NM_001387960, NM_001387962, NM_001387966, NM_001387967, NM_001387968, NM_001387969, NM_001387970, NM_001387971, NM_001387972, NM_001387973, NM_001387974, NM_001387975, NM_001387976, NM_001387977, NM_001387978, NM_001387979, NM_001387980, NM_001387981

CCDS: CCDS43157

Canonical transcript exons

ENST00000321464 — 6 exons

Exon	Start	End
ENSE00002020842	141386872	141386937
ENSE00002046727	141381425	141381487
ENSE00002065552	141403927	141404031
ENSE00002070249	141442389	141449792
ENSE00002086089	141369872	141369946
ENSE00003920043	141368504	141368804

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.2046 / max 1037.2427, expressed in 1805 samples.

FANTOM5 promoters (37 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38909	16.2219	1726
38888	15.0592	1538
38889	7.5608	1249
38899	2.2432	507
38913	2.1031	626
38901	0.9281	143
38897	0.8031	194
38900	0.7614	205
38922	0.6515	204
38887	0.5750	335

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superficial temporal artery	UBERON:0001614	98.01	gold quality
seminal vesicle	UBERON:0000998	97.66	gold quality
pigmented layer of retina	UBERON:0001782	97.40	gold quality
cauda epididymis	UBERON:0004360	97.18	gold quality
stromal cell of endometrium	CL:0002255	97.10	gold quality
jejunal mucosa	UBERON:0000399	97.01	gold quality
jejunum	UBERON:0002115	96.96	gold quality
caput epididymis	UBERON:0004358	96.76	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.73	gold quality
palpebral conjunctiva	UBERON:0001812	96.67	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.57	gold quality
vena cava	UBERON:0004087	96.34	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.29	gold quality
cranial nerve II	UBERON:0000941	96.27	gold quality
colonic epithelium	UBERON:0000397	96.21	gold quality
corpus epididymis	UBERON:0004359	96.05	gold quality
epithelium of nasopharynx	UBERON:0001951	95.92	gold quality
amniotic fluid	UBERON:0000173	95.62	gold quality
colonic mucosa	UBERON:0000317	95.57	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.55	gold quality
gall bladder	UBERON:0002110	95.53	gold quality
heart right ventricle	UBERON:0002080	95.51	gold quality
pericardium	UBERON:0002407	95.39	gold quality
lower lobe of lung	UBERON:0008949	95.34	gold quality
smooth muscle tissue	UBERON:0001135	95.33	gold quality
skin of hip	UBERON:0001554	95.30	gold quality
biceps brachii	UBERON:0001507	95.29	gold quality
corpus callosum	UBERON:0002336	95.24	gold quality
visceral pleura	UBERON:0002401	95.23	gold quality
trigeminal ganglion	UBERON:0001675	95.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	16.05
E-MTAB-8911	no	235.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
CALCA
CBFA2T3
HP
MYOG
TH	Activation

miRNA regulators (miRDB)

156 targeting ZBTB38, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4666A-3P	99.96	71.71	3434

Literature-anchored findings (GeneRIF, showing 13)

• ZBTB38 binds methylated methylated CpGs in vitro and in vivo and represses transcrption. (PMID:16354688)
• There was strongest association with SNPs in the ZBTB38 gene and adult human height. (PMID:18391951)
• Alternative splicing of human height-related zinc finger and BTB domain-containing 38 gene through Alu exonization (PMID:21188497)
• The nonsynonymous SNP (rs16851435:T > G,p.Ser319Ala) of ZBTB38 contributed to susceptibility of idiopathic short stature in the Chinese Han population. (PMID:23302005)
• ZBTB38 regulates replication efficiency by controlling MCM10 transcription. (PMID:24726359)
• rescue of Zbtb38 can alleviate secondary damage of spinal cord through inhibition of ER stress-associated apoptosis, which provides a novel therapeutic regimen that targeting Zbtb38 may promote functional recovery of spinal cord for patients with SCI. (PMID:28514761)
• The SNP of ZBTB38-RASA2 was significantly related with the appearance of myoclonus in sporadic Creutzfeldt-Jacob disease patients. (PMID:29216791)
• A model for the C-terminal ZBTB38 Zinc Fingers in complex with its cognate DNA target is proposed, providing insight into a possible novel mode of methylated DNA recognition. (PMID:29287967)
• The USP9X/ZBTB38 axis limits, senses and detoxifies reactive oxygen species, and provide a molecular link between oxidative stress and the epigenome. (PMID:29490077)
• Results show that ZBTB38 knockdown significantly inhibits autophagic expression and downregulates RB1CC1 expression in SHSY5Y cells. Its overexpression upregulates RB1CC1 expression and enhances autophagy in spinal cord injury mice model. (PMID:30075197)
• the mechanism by which this ZF domain of ZBTB38 selectively recognizes methylated CpG sites (PMID:30355731)
• Study findings suggested that ZBTB38 promoted migration and invasive growth of bladder cancer cells through facilitation of the Wnt/betacatenin signaling pathway. (PMID:30569128)
• Context-dependent CpG methylation directs cell-specific binding of transcription factor ZBTB38. (PMID:36000449)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zbtb38	ENSMUSG00000040433
rattus_norvegicus	Zbtb38	ENSRNOG00000012386
caenorhabditis_elegans		WBGENE00005008
caenorhabditis_elegans		WBGENE00006827
caenorhabditis_elegans		WBGENE00011924
caenorhabditis_elegans		WBGENE00011925

Paralogs (2): ZBTB4 (ENSG00000174282), ZNF438 (ENSG00000183621)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 38 — Q8NAP3 (reviewed: Q8NAP3)

All UniProt accessions (12): A0A1B0GV48, D6R9I1, D6R9J6, D6R9U6, D6RAC4, D6RBC4, D6RC86, D6RE69, D6RGK1, D6RHD1, D6RJE1, Q8NAP3

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator with bimodal DNA-binding specificity. Binds with a higher affinity to methylated CpG dinucleotides in the consensus sequence 5’-CGCG-3’ but can also bind to E-box elements (5’-CACGTG-3’). Can also bind specifically to a single methyl-CpG pair. Represses transcription in a methyl-CpG-dependent manner. Plays an important role in regulating DNA replication and common fragile sites (CFS) stability in a RBBP6- and MCM10-dependent manner; represses expression of MCM10 which plays an important role in DNA-replication. Acts as a transcriptional activator. May be involved in the differentiation and/or survival of late postmitotic neurons.

Subunit / interactions. Interacts with CBFA2T3. Interacts with ZBTB4. Interacts with RBBP6.

Subcellular location. Nucleus. Chromosome.

Post-translational modifications. Ubiquitinated by RBBP6; leading to its degradation by the proteasome.

Domain organisation. The BTB domain is not required for activation of transcription or self-association.

Polymorphism. Genetic variations in ZBTB38 define the stature quantitative trait locus 10 (STQTL10) [MIM:612221]. Adult height is an easily observable and highly heritable complex continuous trait. Because of this, it is a model trait for studying genetic influence on quantitative traits.

RefSeq proteins (85): NP_001073881, NP_001337028, NP_001337029, NP_001363041, NP_001363042, NP_001363043, NP_001363044, NP_001363045, NP_001363046, NP_001363047, NP_001363048, NP_001363049, NP_001363050, NP_001363051, NP_001363052, NP_001363053, NP_001363054, NP_001363055, NP_001363056, NP_001363057, NP_001363071, NP_001363072, NP_001363079, NP_001363081, NP_001363086, NP_001363087, NP_001363088, NP_001363089, NP_001363090, NP_001363091, NP_001363092, NP_001363093, NP_001363094, NP_001363095, NP_001363096, NP_001363097, NP_001363098, NP_001363099, NP_001363100, NP_001363101, NP_001363102, NP_001363103, NP_001363104, NP_001363105, NP_001363106, NP_001363107, NP_001363108, NP_001363109, NP_001363110, NP_001363111, NP_001363112, NP_001363113, NP_001363114, NP_001363115, NP_001363116, NP_001363117, NP_001363118, NP_001363119, NP_001374870, NP_001374874, NP_001374876, NP_001374877, NP_001374879, NP_001374881, NP_001374882, NP_001374886, NP_001374888, NP_001374889, NP_001374891, NP_001374895, NP_001374896, NP_001374897, NP_001374898, NP_001374899, NP_001374900, NP_001374901, NP_001374902, NP_001374903, NP_001374904, NP_001374905, NP_001374906, NP_001374907, NP_001374908, NP_001374909, NP_001374910 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF00651

UniProt features (67 total): cross-link 29, zinc finger region 10, region of interest 5, strand 5, sequence variant 4, helix 4, compositionally biased region 3, turn 3, modified residue 2, chain 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6E94	X-RAY DIFFRACTION	1.59
6E93	X-RAY DIFFRACTION	1.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NAP3-F1	44.37	0.03

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 (31): 130, 309, 43, 145, 148, 151, 259, 550, 557, 754, 758, 763, 804, 814, 821, 842, 850, 857, 923, 964 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 167 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, WANG_RECURRENT_LIVER_CANCER_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, WEI_MYCN_TARGETS_WITH_E_BOX, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_DNA_DAMAGE_RESPONSE, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, CAIRO_HEPATOBLASTOMA_UP, SENESE_HDAC1_TARGETS_UP, BERNARD_PPAPDC1B_TARGETS_UP, CUI_TCF21_TARGETS_2_DN, GOBP_DNA_REPLICATION, GOCC_BLOOD_MICROPARTICLE, GOBP_DNA_METABOLIC_PROCESS

GO Biological Process (5): regulation of DNA replication (GO:0006275), regulation of DNA-templated transcription (GO:0006355), DNA damage response (GO:0006974), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), methyl-CpG binding (GO:0008327), protein homodimerization activity (GO:0042803), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), blood microparticle (GO:0072562)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
regulation of DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
DNA replication	1
regulation of DNA metabolic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular response to stress	1
negative regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
nucleotide binding	1
sequence-specific DNA binding	1
identical protein binding	1
protein dimerization activity	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
extracellular region	1

Protein interactions and networks

STRING

1282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB38	RBBP6	Q7Z6E9	800
ZBTB38	UHRF2	Q96PU4	663
ZBTB38	MGMT	P16455	641
ZBTB38	RAPSN	Q13702	595
ZBTB38	ZBTB4	Q9P1Z0	586
ZBTB38	CTNND2	Q9UQB3	575
ZBTB38	MBD4	O95243	572
ZBTB38	UHRF1	Q96T88	571
ZBTB38	ZBTB33	Q86T24	570
ZBTB38	RASA2	Q15283	540
ZBTB38	CTNND1	O60716	513
ZBTB38	CTBP1	Q13363	508
ZBTB38	CRBN	Q96SW2	494
ZBTB38	MECP2	P51608	492
ZBTB38	CBFA2T3	O75081	473

IntAct

33 interactions, top by confidence:

A	B	Type	Score
ZBTB38	SIRT1	psi-mi:“MI:0915”(physical association)	0.620
ZBTB38	TPP1	psi-mi:“MI:0915”(physical association)	0.560
ZBTB38	DNM2	psi-mi:“MI:0915”(physical association)	0.560
ZBTB38	CARF	psi-mi:“MI:0915”(physical association)	0.560
ZBTB38	IPO7	psi-mi:“MI:0914”(association)	0.530
ZBTB38	E2	psi-mi:“MI:0915”(physical association)	0.490
ZMYND11	ZBTB38	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1CA	ZBTB38	psi-mi:“MI:0407”(direct interaction)	0.440
ZBTB38	iglC2	psi-mi:“MI:0915”(physical association)	0.370
CCL1	ZBTB38	psi-mi:“MI:0915”(physical association)	0.370
Mis12		psi-mi:“MI:0914”(association)	0.350
ZBTB38	NEMF	psi-mi:“MI:0914”(association)	0.350
ZBTB38	E2	psi-mi:“MI:0915”(physical association)	0.000
EPHA1	ZBTB38	psi-mi:“MI:0915”(physical association)	0.000
FMR1	ZBTB38	psi-mi:“MI:0915”(physical association)	0.000
KCNJ6	ZBTB38	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	ZBTB38	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (183): ZBTB38 (Two-hybrid), ZBTB38 (Two-hybrid), ZBTB38 (Two-hybrid), ZBTB38 (Two-hybrid), ZBTB38 (Two-hybrid), ZBTB38 (Two-hybrid), ZBTB38 (Two-hybrid), ZBTB38 (Two-hybrid), ZBTB38 (Two-hybrid), ZBTB38 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), RPL26L1 (Affinity Capture-MS), YTHDC2 (Affinity Capture-MS), POP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5NS60, A0JN76, A1YFX5, A2T7G6, A6NJL1, D2HQI1, F1MJR8, O14901, P0CG00, P10754, P22227, P98182, Q0IJ29, Q1L8W0, Q3SWU4, Q5DW34, Q5EAC5, Q5EXX3, Q5RHB5, Q5SXI5, Q5T619, Q66H04, Q6NRM8, Q6NV66, Q6ZSB9, Q7M6U3, Q7TS63, Q7TSH3, Q7ZWZ4, Q801P1, Q86VK4, Q8BKX7, Q8BXX2, Q8NAM6, Q8NAP3, Q8NCP5, Q8R0A2, Q91VW9, Q96IT1, Q96N77

Diamond homologs: A0A1B8YAB1, A1YPR0, B0WWP2, B1H285, B3M9V8, B3NDN0, B4GRJ2, B4HIK1, B4J045, B4L0G9, B4LIG6, B4MXW3, B4PD06, B4QLQ2, C9JR72, D3Z8N4, E0CZ16, G3X9X1, O15062, O88939, O93567, O95365, P28575, P41182, P41183, Q08CL3, Q08DK3, Q13105, Q16RL8, Q2M0J9, Q3UQV5, Q52KB5, Q5EXX3, Q5R7B8, Q5RDY3, Q5TC79, Q5ZI33, Q5ZKD9, Q5ZM39, Q60821

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RBBP6	“down-regulates quantity by destabilization”	ZBTB38	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	110
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

964 predictions. Top by Δscore:

Variant	Effect	Δscore
3:141403994:G:GT	donor_gain	1.0000
3:141402445:GCCCC:G	donor_gain	0.9900
3:141402450:G:GG	donor_gain	0.9900
3:141403976:A:AG	donor_gain	0.9900
3:141402446:CCCC:C	donor_gain	0.9800
3:141402447:CCCG:C	donor_loss	0.9800
3:141402448:CC:C	donor_gain	0.9800
3:141402448:CCGTA:C	donor_loss	0.9800
3:141402449:CG:C	donor_loss	0.9800
3:141402450:G:T	donor_loss	0.9800
3:141402451:T:TC	donor_loss	0.9800
3:141403977:T:G	donor_gain	0.9800
3:141403995:A:T	donor_gain	0.9800
3:141442382:GTTTC:G	acceptor_loss	0.9800
3:141442385:TCAG:T	acceptor_loss	0.9800
3:141442387:A:AC	acceptor_loss	0.9800
3:141402447:CCC:C	donor_gain	0.9700
3:141442387:A:AG	acceptor_gain	0.9700
3:141442388:G:GG	acceptor_gain	0.9700
3:141442388:GAT:G	acceptor_gain	0.9700
3:141404018:C:A	donor_gain	0.9600
3:141387884:ACAGG:A	donor_loss	0.9300
3:141387889:T:A	donor_loss	0.9300
3:141402643:G:GT	donor_gain	0.9300
3:141403921:TTTTA:T	acceptor_loss	0.9300
3:141403922:TTTAG:T	acceptor_loss	0.9300
3:141403923:TTAG:T	acceptor_loss	0.9300
3:141403924:TA:T	acceptor_loss	0.9300
3:141402452:AAGT:A	donor_loss	0.9200
3:141404010:AAGCT:A	donor_gain	0.9100

AlphaMissense

7984 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:141442675:T:A	V96D	1.000
3:141443856:T:C	C490R	1.000
3:141443857:G:A	C490Y	1.000
3:141443858:C:G	C490W	1.000
3:141443866:G:A	C493Y	1.000
3:141443867:C:G	C493W	1.000
3:141443877:T:C	F497L	1.000
3:141443878:T:C	F497S	1.000
3:141443879:T:A	F497L	1.000
3:141443879:T:G	F497L	1.000
3:141443940:T:C	C518R	1.000
3:141443942:C:G	C518W	1.000
3:141443949:T:C	C521R	1.000
3:141443951:T:G	C521W	1.000
3:141443961:T:C	F525L	1.000
3:141443963:C:A	F525L	1.000
3:141443963:C:G	F525L	1.000
3:141443980:T:C	L531P	1.000
3:141445611:T:C	F1075L	1.000
3:141445613:C:A	F1075L	1.000
3:141445613:C:G	F1075L	1.000
3:141442456:T:C	L23S	0.999
3:141442498:T:A	I37N	0.999
3:141442651:T:C	L88P	0.999
3:141442681:T:A	V98D	0.999
3:141442708:T:C	L107P	0.999
3:141443772:T:C	C462R	0.999
3:141443774:C:G	C462W	0.999
3:141443781:T:A	C465S	0.999
3:141443781:T:C	C465R	0.999

dbSNP variants (sampled 300 via entrez): RS1000007375 (3:141368484 C>G,T), RS1000024639 (3:141377641 T>G), RS1000035247 (3:141330417 TGG>T), RS1000108057 (3:141407390 T>G), RS1000109564 (3:141423880 A>T), RS1000161670 (3:141439408 C>T), RS1000170374 (3:141421353 T>C), RS1000198951 (3:141322909 A>G), RS1000295861 (3:141337044 G>A), RS1000311157 (3:141368264 T>C), RS1000311797 (3:141414493 T>C), RS1000321817 (3:141400841 T>A,C), RS1000346366 (3:141429891 G>A), RS1000379686 (3:141345446 T>C,G), RS1000381478 (3:141330271 A>C,G)

Disease associations

OMIM: gene MIM:612218 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

136 associations (top):

Study	Trait	p-value
GCST000136_3	Height	1.000000e-06
GCST000174_20	Height	2.000000e-24
GCST000175_28	Height	1.000000e-27
GCST000176_18	Height	8.000000e-22
GCST000372_7	Height	3.000000e-12
GCST000380_2	Height	6.000000e-12
GCST000522_8	Height	8.000000e-08
GCST000611_19	Height	6.000000e-09
GCST000817_65	Height	3.000000e-86
GCST001148_6	Prostate cancer	2.000000e-08
GCST001263_25	Height	2.000000e-10
GCST001366_2	Prion diseases	2.000000e-06
GCST001956_20	Height	4.000000e-47
GCST002608_4	Pulmonary function in asthmatics	4.000000e-06
GCST002646_13	Infant length	4.000000e-07
GCST002647_94	Height	3.000000e-158
GCST002702_40	Height	6.000000e-34
GCST003457_5	Soluble receptor for advanced glycation end-product levels	8.000000e-06
GCST003997_34	Myopia	8.000000e-19
GCST004063_143	Waist circumference adjusted for body mass index	1.000000e-11
GCST004063_150	Waist circumference adjusted for body mass index	4.000000e-13
GCST004065_88	Waist circumference	3.000000e-10
GCST004065_92	Waist circumference	1.000000e-06
GCST004066_142	Hip circumference	2.000000e-11
GCST004066_28	Hip circumference	3.000000e-16
GCST004066_78	Hip circumference	5.000000e-24
GCST004067_108	Hip circumference adjusted for BMI	8.000000e-43
GCST004067_146	Hip circumference adjusted for BMI	1.000000e-26
GCST004067_40	Hip circumference adjusted for BMI	2.000000e-22
GCST004094_6	Prostate-specific antigen levels (conditioned on lead SNPs)	3.000000e-11

EFO canonical traits (27, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004314	forced expiratory volume
EFO:0006785	infant body height
EFO:0007819	advanced glycation end-product measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0004305	erythrocyte count
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0004847	age at onset
EFO:0009270	heel bone mineral density
EFO:0003924	hair color
EFO:0004341	body fat distribution
EFO:0004338	body weight
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0010473	cyclic adenosine monophosphate measurement
EFO:0004509	hemoglobin measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004980	appendicular lean mass
EFO:0004348	hematocrit
EFO:0007990	neutrophil percentage of leukocytes
EFO:0006941	grip strength measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases mutagenesis	6
Tetrachlorodibenzodioxin	increases expression, affects expression	5
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	4
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	3
(+)-JQ1 compound	decreases expression	2
Acetaminophen	decreases expression, affects response to substance	2
Cadmium Chloride	increases expression	2
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
arsenite	decreases reaction, affects binding	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
belinostat	decreases expression	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1

Clinical trials (associated diseases)

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