HOPX

Summary

HOPX (HOP homeobox, HGNC:24961) is a protein-coding gene on chromosome 4q12, encoding Homeodomain-only protein (Q9BPY8). Atypical homeodomain protein which does not bind DNA and is required to modulate cardiac growth and development.

The protein encoded by this gene is a homeodomain protein that lacks certain conserved residues required for DNA binding. It was reported that choriocarcinoma cell lines and tissues failed to express this gene, which suggested the possible involvement of this gene in malignant conversion of placental trophoblasts. Studies in mice suggest that this protein may interact with serum response factor (SRF) and modulate SRF-dependent cardiac-specific gene expression and cardiac development. Multiple alternatively spliced transcript variants have been identified for this gene.

Source: NCBI Gene 84525 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_032495

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24961
Approved symbol	HOPX
Name	HOP homeobox
Location	4q12
Locus type	gene with protein product
Status	Approved
Aliases	LAGY, HOP, OB1, NECC1, SMAP31
Ensembl gene	ENSG00000171476
Ensembl biotype	protein_coding
OMIM	607275
Entrez	84525

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 20 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000317745, ENST00000337881, ENST00000381255, ENST00000381260, ENST00000420433, ENST00000503639, ENST00000503864, ENST00000506661, ENST00000508121, ENST00000553379, ENST00000554144, ENST00000555760, ENST00000556376, ENST00000556614, ENST00000605395, ENST00000867399, ENST00000867400, ENST00000867401, ENST00000867402, ENST00000960483, ENST00000960484, ENST00000960485, ENST00000960486

RefSeq mRNA: 5 — MANE Select: NM_032495 NM_001145459, NM_001145460, NM_032495, NM_139211, NM_139212

CCDS: CCDS3507, CCDS47062, CCDS54767

Canonical transcript exons

ENST00000420433 — 4 exons

Exon	Start	End
ENSE00001487985	56681255	56681296
ENSE00003463578	56657775	56657899
ENSE00003584891	56647998	56648797
ENSE00003634770	56655857	56656012

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 99.85.

FANTOM5 (CAGE): breadth broad, TPM avg 16.8789 / max 962.8565, expressed in 635 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52213	9.4273	297
52203	2.1946	296
52205	1.6994	397
52206	1.0858	289
52202	0.8634	96
52214	0.5508	92
52216	0.2362	79
52207	0.1829	80
52217	0.1231	73
52211	0.1211	60

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	99.85	gold quality
corpus epididymis	UBERON:0004359	99.77	gold quality
lower esophagus mucosa	UBERON:0035834	99.75	gold quality
skin of hip	UBERON:0001554	99.73	gold quality
pharyngeal mucosa	UBERON:0000355	99.70	gold quality
penis	UBERON:0000989	99.67	gold quality
oral cavity	UBERON:0000167	99.65	gold quality
skin of abdomen	UBERON:0001416	99.56	gold quality
tongue squamous epithelium	UBERON:0006919	99.53	gold quality
mammalian vulva	UBERON:0000997	99.48	gold quality
skin of leg	UBERON:0001511	99.45	gold quality
zone of skin	UBERON:0000014	99.42	gold quality
right lung	UBERON:0002167	99.41	gold quality
upper lobe of left lung	UBERON:0008952	99.39	gold quality
upper lobe of lung	UBERON:0008948	99.38	gold quality
gingiva	UBERON:0001828	99.33	gold quality
body of tongue	UBERON:0011876	99.29	gold quality
gingival epithelium	UBERON:0001949	99.21	gold quality
amniotic fluid	UBERON:0000173	99.20	gold quality
nipple	UBERON:0002030	99.11	gold quality
lower lobe of lung	UBERON:0008949	99.06	gold quality
adult organism	UBERON:0007023	98.94	gold quality
middle temporal gyrus	UBERON:0002771	98.86	gold quality
right lobe of thyroid gland	UBERON:0001119	98.85	gold quality
palpebral conjunctiva	UBERON:0001812	98.82	gold quality
left lobe of thyroid gland	UBERON:0001120	98.79	gold quality
esophagus mucosa	UBERON:0002469	98.68	gold quality
cingulate cortex	UBERON:0003027	98.65	gold quality
thyroid gland	UBERON:0002046	98.63	gold quality
cervix epithelium	UBERON:0004801	98.63	gold quality

Single-cell (SCXA)

Detected in 42 experiment(s), a significant marker in 37.

Experiment	Marker?	Max mean expression
E-MTAB-8221	yes	12239.96
E-HCAD-15	yes	5398.91
E-CURD-126	yes	4586.84
E-HCAD-24	yes	2206.33
E-MTAB-6701	yes	1923.49
E-MTAB-6308	yes	1874.89
E-MTAB-6653	yes	1671.77
E-MTAB-8884	yes	1640.63
E-MTAB-9435	yes	1525.57
E-MTAB-11121	yes	1398.12
E-MTAB-8271	yes	1072.82
E-MTAB-8207	yes	1070.14
E-GEOD-86618	yes	949.55
E-CURD-122	yes	690.70
E-MTAB-10432	yes	618.55

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

9 targets.

Target	Regulation
DHX9
FKBP4
FLG	Activation
FOS	Repression
HSP90AB1
LORICRIN	Activation
MMP1
NPPA
NPPB

Upstream regulators (CollecTRI, top): HSF1, NKX2-5, SRF

miRNA regulators (miRDB)

42 targeting HOPX, 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-1252-5P	100.00	69.80	2774
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-876-3P	98.76	68.23	945

Literature-anchored findings (GeneRIF, showing 40)

• Loss of NECC1 expression is involved in malignant conversion of placental trophoblasts. (PMID:12573257)
• Gene mapping locates LAGY on chromosome 4q11-13.1. In 72 primary lung tumors, this gene was significantly down-regulated compared to 9 normal lung tissue samples. (PMID:12759545)
• One role of Hop is to modify the expression of cardiac-specific genes and thereby finely regulate heart development. (PMID:14522464)
• Decrease in homeodomain-only protein is associated with hypopharyngeal carcinoma (PMID:15213722)
• SMAP31 expression is elevated in 4 of 6 papillary thyroid tumor samples compared to 4 normal thyroid controls. (PMID:15307938)
• loss of NECC1 expression is involved in malignant conversion of placental trophoblasts (PMID:15457851)
• Our results demonstrate that the homeodomain fold has been co-opted during evolution for functions other than sequence-specific DNA binding and suggest that HOP functions as an adaptor protein to mediate transcriptional repression. (PMID:16939210)
• The data indicate that signaling induced by hop/STI-1 depends on endocytosis (PMID:17498662)
• Gradual induction of HOP/NECC1 in response to differentiation stimuli may result in the decision to differentiate into a particular type of trophoblastic cell lineage and result in non-lethal defects (PMID:17576768)
• C-terminal domain of Harc is a key determinant of its cochaperone functions (PMID:18052042)
• HOP is a putative tumor suppressor gene that harbors tumor inhibitory activity. (PMID:18234960)
• HOP may work as a tumor suppressor in a subset of glioblastomas; HOP function thus appears to be critical in the adult brain in a region of continued plasticity, and its deregulation may contribute to disease (PMID:18507846)
• transcriptional silencing of HOPX results from hypermethylation of the HOPpromoter, which leads to human uterine endometrial cancers (HEC) development. (PMID:19173292)
• HOPX is modulated by cell differentiation in human keratinocytes and this might contribute to homeostasis of keratinocytes by controlling differentiation-dependent genes. (PMID:20226564)
• HOPX-beta promoter methylation is a frequent and cancer-specific event in gastric cancer (PMID:20228841)
• Hopx regulates the expression of genes involved in regulation of apoptosis and survival and makes them refractory to Fas-induced apoptosis. (PMID:21061432)
• HOP is a novel modulator of late terminal differentiation in keratinocytes (PMID:21256618)
• HOPX/Hopx expression is reduced in multiple examples of human and murine cardiac hypertrophy and failure. (PMID:21382376)
• results identify distinct functions for the Hop cochaperone, revealing an asymmetric mechanism for Hsp90 regulation and client loading (PMID:21700222)
• HOPX-beta promoter methylation is a frequent and cancer-specific event in CRC progression. (PMID:22904674)
• Knockdown of Hop caused a decrease in the level of RhoC GTPase, and significantly inhibited pseudopodia formation in Hs578T cells. Our data suggest that Hop regulates directional cell migration by multiple unknown mechanisms. (PMID:23036489)
• GATA6 and HOPX are critical nodes in a lineage-selective pathway that directly links effectors of airway epithelial specification to the inhibition of metastasis in the lung ADC subtype. (PMID:23707782)
• The results suggest that HOPX may contribute to pathogenesis or manifestation of hypertrophic cardiomyopathy as a modifier gene. (PMID:25036325)
• HOPX is methylated and exerts tumour-suppressive function through Ras-induced senescence in human lung cancer. (PMID:25345926)
• Data show that binding of heat shock proteins Hsp70 and Hsp90 requires prior binding of Hop protein to Hsp90. (PMID:26286954)
• HOPX has a role in the pathogenesis of skin cancers and skin diseases. (PMID:27017330)
• these data indicate that the disruption of the PrP(C)-HOP complex could be a potential therapeutic target for modulating the migratory and invasive cellular properties that lead to metastatic Colorectal cancer (CRC). (PMID:27112151)
• Computational results identified HOPX gene as a new potential driver for ovarian carcinogenesis. (PMID:27287041)
• HOPX promoter methylation is not only frequent and cancer-specific but also associated with aggressive phenotype in breast cancer. (PMID:27756570)
• HOPX functions as a tumour suppressor in HNSCC and suggest a central role for HOPX in suppressing epithelial carcinogenesis (PMID:27934959)
• Data suggest that HOP homeobox HOPX (HOPX) acts as a tumour suppressor via the epigenetic regulation of snail family transcription factors (SNAIL) transcription and a prognostic biomarker for nasopharyngeal carcinoma (NPC) metastasis and therapeutic target for NPC treatment. (PMID:28146149)
• HOPX is a distinctive homeobox gene with characteristic clinical and biological implications and its expression is a powerful predictor of prognosis in AML patients. (PMID:28341738)
• The association between the MEEVD C-terminal peptide from the heat shock protein 90 (Hsp90) and tetratricopeptide repeat A (TPR2A) domain of the heat shock organizing protein (Hop) is a useful prototype to study the fundamental molecular details about the Hop-Hsp90 interaction. Observed are conformational changes of the peptide and the protein receptor induced by binding. The binding free energy is 8.4 kcal/mol. (PMID:28723223)
• HOPX is functionally regulated by SCL in hematoendothelial differentiation of mesoderm progenitor cells. (PMID:28813672)
• In idiopathic pulmonary fibrosis lungs, HOPX expression was decreased in whole lungs and significantly correlated to a decline in lung function and progression of IPF. HOPX is upregulated during early alveolar injury and repair process in the lung. Decreased HOPX expression might contribute to failed regenerative processes in end-stage IPF lungs. (PMID:30154568)
• The hypertrophic signaling is not effectively activated during monolayer-based cardiac differentiation, thereby preventing expression of HOPX and its activation of downstream genes that govern late stages of cardiomyocyte maturation. (PMID:30290179)
• Study revealed that ZNF750 is both necessary and sufficient for HOPX induction and propose that HOPX functions as a positive regulator of epidermal late differentiation within a p63-ZNF750-HOPX pathway to up-regulate the key proteins required for terminal epidermal differentiation, providing clarity to previous studies showing conflicting results. (PMID:30959041)
• In the present study, we compared the 2 potential epigenetic prognostic markers of CDO1 hypermethylation and HOPX hypermethylation using the same breast cancer samples, and the final focus was given on CDO1 hypermethylation (PMID:31092420)
• These data indicated that miR421 may act as an oncogene through the effects of HOPX on the Wnt/bcatenin signaling pathway and may provide insight into the mechanisms underlying carcinogenesis and the identification of potential biomarkers associated with nonsmall cell lung cancer (NSCLC). (PMID:31115507)
• HOPX regulates bone marrow-derived mesenchymal stromal cell fate determination via suppression of adipogenic gene pathways. (PMID:32647304)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hopx	ENSDARG00000089368
mus_musculus	Hopx	ENSMUSG00000059325
rattus_norvegicus	Hopx	ENSRNOG00000024689
caenorhabditis_elegans		WBGENE00009231

Protein

Protein identifiers

Homeodomain-only protein — Q9BPY8 (reviewed: Q9BPY8)

Alternative names: Lung cancer-associated Y protein, Not expressed in choriocarcinoma protein 1, Odd homeobox protein 1

All UniProt accessions (1): Q9BPY8

UniProt curated annotations — full annotation on UniProt →

Function. Atypical homeodomain protein which does not bind DNA and is required to modulate cardiac growth and development. Acts via its interaction with SRF, thereby modulating the expression of SRF-dependent cardiac-specific genes and cardiac development. Prevents SRF-dependent transcription either by inhibiting SRF binding to DNA or by recruiting histone deacetylase (HDAC) proteins that prevent transcription by SRF. Overexpression causes cardiac hypertrophy. May act as a tumor suppressor. Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and assists in chaperone-mediated protein refolding.

Subunit / interactions. Interacts with serum response factor (SRF). Component of a large complex containing histone deacetylases such as HDAC2. Interacts with the acetylated forms of HSPA1A and HSPA1B. Interacts with HSPA8.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Widely expressed. Expressed in the heart, brain, placenta, lung, skeletal and smooth muscles, uterus, urinary bladder, kidney and spleen. Down-regulated in some types of cancer such as lung cancer, choriocarcinoma, head and neck squamous cell carcinoma and oral squamous cell carcinoma.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BPY8-1	1, A	yes
Q9BPY8-2	2, B
Q9BPY8-3	3
Q9BPY8-4	4

RefSeq proteins (5): NP_001138931, NP_001138932, NP_115884, NP_631957, NP_631958 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR039162	HOPX	Family

Pfam: PF00046

UniProt features (6 total): splice variant 2, sequence conflict 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BPY8-F1	83.57	0.58

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9725554	Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin

MSigDB gene sets: 396 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, JAEGER_METASTASIS_DN, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_GROWTH, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGENERATION, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_CHAPERONE_MEDIATED_PROTEIN_COMPLEX_ASSEMBLY

GO Biological Process (13): negative regulation of transcription by RNA polymerase II (GO:0000122), trophectodermal cell differentiation (GO:0001829), bundle of His development (GO:0003166), regulation of transcription by RNA polymerase II (GO:0006357), regulation of heart contraction (GO:0008016), positive regulation of skeletal muscle tissue regeneration (GO:0043415), negative regulation of cell differentiation (GO:0045596), lung alveolus development (GO:0048286), chaperone-mediated protein complex assembly (GO:0051131), positive regulation of striated muscle cell differentiation (GO:0051155), positive regulation of gap junction assembly (GO:1903598), heart development (GO:0007507), cell differentiation (GO:0030154)

GO Molecular Function (3): DNA binding (GO:0003677), histone deacetylase regulator activity (GO:0035033), protein binding (GO:0005515)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Developmental Cell Lineages of the Integumentary System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
cell differentiation	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
blastocyst formation	1
His-Purkinje system development	1
ventricular cardiac muscle tissue development	1
regulation of DNA-templated transcription	1
heart contraction	1
regulation of blood circulation	1
skeletal muscle tissue regeneration	1
regulation of skeletal muscle tissue regeneration	1
positive regulation of developmental growth	1
regulation of cell differentiation	1
negative regulation of cellular process	1
negative regulation of developmental process	1
lung development	1
anatomical structure development	1
protein-containing complex assembly	1
striated muscle cell differentiation	1
positive regulation of muscle cell differentiation	1
regulation of striated muscle cell differentiation	1
gap junction assembly	1
positive regulation of cell junction assembly	1
regulation of gap junction assembly	1
animal organ development	1
circulatory system development	1
cellular developmental process	1
nucleic acid binding	1
histone deacetylase activity	1
enzyme regulator activity	1
histone deacetylase binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1848 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOPX	HDAC2	Q92769	963
HOPX	LRIG1	Q96JA1	743
HOPX	NKX2-5	P52952	738
HOPX	SRF	P11831	729
HOPX	NKX2-1	P43699	694
HOPX	LGR5	O75473	688
HOPX	SFTPC	P11686	669
HOPX	SOX2	P48431	663
HOPX	BMI1	P35226	634
HOPX	R4GMX3	R4GMX3	631
HOPX	FAM107A	O95990	628
HOPX	OLFM4	Q6UX06	597
HOPX	PTPRZ1	P23471	596
HOPX	ASCL2	Q99929	589
HOPX	PAX3	P23760	584

IntAct

12 interactions, top by confidence:

A	B	Type	Score
TCF12	HOPX	psi-mi:“MI:0915”(physical association)	0.560
HOPX	TCF12	psi-mi:“MI:0915”(physical association)	0.560
HOPX	PICK1	psi-mi:“MI:0915”(physical association)	0.560
HOPX	INTS13	psi-mi:“MI:0915”(physical association)	0.400
HOPX	PTGER4	psi-mi:“MI:0915”(physical association)	0.370
HOPX	ZSCAN1	psi-mi:“MI:0915”(physical association)	0.370
TLX3	HOPX	psi-mi:“MI:0915”(physical association)	0.370
HOXB9	HOPX	psi-mi:“MI:0915”(physical association)	0.370
HOPX	PICK1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): HOPX (Two-hybrid), HOPX (Affinity Capture-Western), HOPX (Affinity Capture-Western), ASUN (Affinity Capture-MS), HDAC2 (Affinity Capture-Western), HOPX (Positive Genetic), HOPX (Two-hybrid), HOPX (Two-hybrid), HOPX (Affinity Capture-Western), HOPX (Two-hybrid), HOPX (Two-hybrid), HOPX (Two-hybrid), ZSCAN1 (Two-hybrid), HOPX (Affinity Capture-Western), HOPX (Affinity Capture-Western)

ESM2 similar proteins: A0A2R8QFQ6, A7MB28, E2R222, G3MWR8, O88508, O95544, P18031, P20417, P35790, P58058, Q01134, Q12800, Q12841, Q13042, Q1LZ53, Q28D01, Q2MHE5, Q4V860, Q4W5Z4, Q58D84, Q5R9Y1, Q5RA95, Q62356, Q62632, Q64143, Q6AYR2, Q6NZH6, Q6PKX4, Q78ZR5, Q7RTP6, Q7T2U9, Q7Z6J6, Q86XW9, Q8BTG7, Q8CJ19, Q8JHU0, Q8MJD5, Q8MJD6, Q8NBA8, Q8R1H0

Diamond homologs: A1YEY5, A1YFI3, A1YG57, A2T733, A2T7P4, O15499, P29454, P53544, P53545, P53546, P54366, P56915, Q02591, Q78ZR5, Q8AYB8, Q8JHU0, Q8MJD5, Q8MJD6, Q8R1H0, Q9BPY8, Q9D6J1, A2X7U1, A2YWC0, O18400, O23208, O35160, O75364, O93385, P46667, P46668, P56673, P70314, P78337, P81062, P97474, Q5E9R6, Q6H6S3, Q6K498, Q6QU75, Q6Z248

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
HOPX	“up-regulates quantity by expression”	FLG	“transcriptional regulation”
HOPX	“up-regulates quantity by expression”	LORICRIN	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1079 predictions. Top by Δscore:

Variant	Effect	Δscore
4:56655852:CGCA:C	donor_loss	1.0000
4:56655853:GCA:G	donor_loss	1.0000
4:56655854:CAC:C	donor_loss	1.0000
4:56655855:A:C	donor_loss	1.0000
4:56656009:CGCG:C	acceptor_gain	1.0000
4:56659291:A:AC	donor_gain	1.0000
4:56659292:C:CC	donor_gain	1.0000
4:56659301:T:TA	donor_gain	1.0000
4:56659338:T:A	donor_gain	1.0000
4:56659369:T:TA	donor_gain	1.0000
4:56659412:C:A	donor_gain	1.0000
4:56648793:CATTT:C	acceptor_gain	0.9900
4:56648795:TTT:T	acceptor_gain	0.9900
4:56648795:TTTC:T	acceptor_loss	0.9900
4:56648797:TC:T	acceptor_loss	0.9900
4:56648798:C:CC	acceptor_gain	0.9900
4:56648799:T:C	acceptor_loss	0.9900
4:56655855:A:AC	donor_gain	0.9900
4:56655856:C:CC	donor_gain	0.9900
4:56655867:T:TA	donor_gain	0.9900
4:56655925:TGTCG:T	donor_gain	0.9900
4:56656008:GCGCG:G	acceptor_gain	0.9900
4:56656009:CGCGC:C	acceptor_gain	0.9900
4:56656010:GCG:G	acceptor_gain	0.9900
4:56656011:CG:C	acceptor_gain	0.9900
4:56656011:CGC:C	acceptor_gain	0.9900
4:56656012:GCTG:G	acceptor_loss	0.9900
4:56656013:C:CC	acceptor_gain	0.9900
4:56656013:C:CG	acceptor_loss	0.9900
4:56656014:T:G	acceptor_loss	0.9900

AlphaMissense

581 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:56648790:A:G	F51S	0.993
4:56648794:A:G	W50R	0.993
4:56648794:A:T	W50R	0.993
4:56648789:A:C	F51L	0.992
4:56648789:A:T	F51L	0.992
4:56648791:A:G	F51L	0.992
4:56655938:G:C	F21L	0.992
4:56655938:G:T	F21L	0.992
4:56655940:A:G	F21L	0.992
4:56648792:C:A	W50C	0.991
4:56648792:C:G	W50C	0.991
4:56655892:C:G	A37P	0.991
4:56648768:C:A	W58C	0.988
4:56648768:C:G	W58C	0.988
4:56655876:A:G	L42P	0.988
4:56655939:A:G	F21S	0.987
4:56648766:C:G	R59P	0.986
4:56648781:C:G	R54P	0.986
4:56655951:A:T	L17Q	0.986
4:56648755:C:G	G63R	0.985
4:56655883:C:G	A40P	0.985
4:56655889:C:G	A38P	0.985
4:56648770:A:G	W58R	0.983
4:56648770:A:T	W58R	0.983
4:56655891:G:T	A37E	0.983
4:56655894:A:T	I36N	0.982
4:56655951:A:G	L17P	0.981
4:56648782:G:T	R54S	0.979
4:56655888:G:T	A38D	0.979
4:56655897:A:G	L35P	0.979

dbSNP variants (sampled 300 via entrez): RS1000040971 (4:56649886 A>G), RS1000187458 (4:56675254 T>C), RS1000190271 (4:56656181 G>A), RS1000237542 (4:56668584 G>C), RS1000416581 (4:56661543 T>C), RS10004220 (4:56680711 T>A,C), RS1000468274 (4:56668114 G>A), RS1000490598 (4:56655124 G>A,C), RS1000497302 (4:56649656 C>T), RS1000542390 (4:56654709 T>G), RS1000574811 (4:56669774 T>C), RS1000627124 (4:56670080 C>T), RS1000808893 (4:56661746 A>C), RS1000809418 (4:56676531 TTTTTC>T,TTTTTCTTTTC), RS1000898812 (4:56666523 A>G)

Disease associations

OMIM: gene MIM:607275 | disease phenotypes: MIM:614727

GenCC curated gene-disease

Mondo (1): TMEM165-congenital disorder of glycosylation (MONDO:0013870)

Orphanet (1): TMEM165-CDG (Orphanet:314667)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002936_16	Cadmium levels	9.000000e-06
GCST006493_10	Systemic sclerosis	8.000000e-06
GCST90002385_248	High light scatter reticulocyte count	1.000000e-10
GCST90002386_577	High light scatter reticulocyte percentage of red cells	7.000000e-13
GCST90002406_87	Reticulocyte fraction of red cells	9.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	8
methylmercuric chloride	decreases expression	3
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
Estradiol	increases expression, decreases expression, affects expression, affects cotreatment	3
Arsenic Trioxide	decreases expression, increases expression	2
Lipopolysaccharides	affects expression, affects reaction, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	affects cotreatment, increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
GSK-J4	decreases expression	1
UNC1999	decreases expression, decreases reaction	1
urushiol	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
arsenite	decreases expression, increases abundance	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
antimonite	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
Chir 99021	affects cotreatment, increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
archazolid B	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1

Cellosaurus cell lines

7 cell lines: 4 embryonic stem cell, 3 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A2V8	SEES3-1V human HOPX, clone1	Embryonic stem cell	Male
CVCL_A2V9	SEES3-1V human HOPX, clone2	Embryonic stem cell	Male
CVCL_A2W0	SEES3-1V human HOPX, clone3	Embryonic stem cell	Male
CVCL_VM28	RUES2 HOPX KO	Embryonic stem cell	Female
CVCL_VM46	WTC11 HOPX-NLS-eGFP	Induced pluripotent stem cell	Male
CVCL_VQ27	WTC CRISPRi HOPX g1	Induced pluripotent stem cell	Male
CVCL_VQ28	WTC CRISPRi HOPX g4	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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