HDGFL2

Summary

HDGFL2 (HDGF like 2, HGNC:14680) is a protein-coding gene on chromosome 19p13.3, encoding Hepatoma-derived growth factor-related protein 2 (Q7Z4V5). Acts as an epigenetic regulator of myogenesis in cooperation with DPF3a (isoform 2 of DPF3/BAF45C).

This gene encodes a member of the hepatoma-derived growth factor (HDGF) family. The protein includes an N-terminal PWWP domain that binds to methyl-lysine-containing histones, with specific binding of this protein to tri-methylated lysines 36 and 79 of histone H3, and di- and tri-methylated lysine 20 of histone H4. The protein functions in LEDGF/p75-independent HIV-1 replication by determining HIV-1 integration site selection. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 84717 — RefSeq curated summary.

At a glance

• GWAS associations: 30
• Clinical variants (ClinVar): 24 total — 2 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001001520

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14680
Approved symbol	HDGFL2
Name	HDGF like 2
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	HRP2, Hdgfrp2
Ensembl gene	ENSG00000167674
Ensembl biotype	protein_coding
OMIM	617884
Entrez	84717

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 22 protein_coding, 2 nonsense_mediated_decay

ENST00000587016, ENST00000589486, ENST00000592417, ENST00000592691, ENST00000601353, ENST00000614903, ENST00000615225, ENST00000616600, ENST00000619255, ENST00000621835, ENST00000901361, ENST00000901362, ENST00000901363, ENST00000901364, ENST00000901365, ENST00000901366, ENST00000901367, ENST00000940522, ENST00000940523, ENST00000940524, ENST00000940525, ENST00000940526, ENST00000966517, ENST00000966518

RefSeq mRNA: 3 — MANE Select: NM_001001520 NM_001001520, NM_001348169, NM_032631

CCDS: CCDS42472, CCDS59336

Canonical transcript exons

ENST00000616600 — 16 exons

Exon	Start	End
ENSE00001115494	4491764	4491835
ENSE00001115498	4497958	4498031
ENSE00002824976	4499491	4499704
ENSE00003575155	4498306	4498376
ENSE00003624259	4475275	4475351
ENSE00003635568	4475445	4475583
ENSE00003667282	4498814	4498915
ENSE00003678344	4491566	4491682
ENSE00003717577	4493703	4493862
ENSE00003718042	4501911	4502207
ENSE00003722071	4488676	4488876
ENSE00003723516	4494166	4494475
ENSE00003724168	4472297	4472422
ENSE00003735954	4496302	4496405
ENSE00003749447	4501191	4501317
ENSE00003750456	4493982	4494057

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 96.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.2602 / max 158.7819, expressed in 1797 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173352	18.6014	1790
173353	1.1179	381
173354	0.7200	464
173351	0.6007	354
173350	0.1392	27
173349	0.0571	10
173348	0.0239	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	96.88	gold quality
sural nerve	UBERON:0015488	95.97	gold quality
ganglionic eminence	UBERON:0004023	95.59	gold quality
left testis	UBERON:0004533	95.20	gold quality
right testis	UBERON:0004534	94.97	gold quality
cortical plate	UBERON:0005343	94.43	gold quality
tendon of biceps brachii	UBERON:0008188	93.69	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.33	gold quality
gastrocnemius	UBERON:0001388	93.23	gold quality
cerebellar hemisphere	UBERON:0002245	93.07	gold quality
right ovary	UBERON:0002118	93.01	gold quality
cerebellar cortex	UBERON:0002129	93.01	gold quality
muscle of leg	UBERON:0001383	92.90	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.90	gold quality
testis	UBERON:0000473	92.74	gold quality
stromal cell of endometrium	CL:0002255	92.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.51	gold quality
left ovary	UBERON:0002119	92.48	gold quality
body of uterus	UBERON:0009853	92.28	gold quality
apex of heart	UBERON:0002098	92.22	gold quality
adenohypophysis	UBERON:0002196	92.11	gold quality
right uterine tube	UBERON:0001302	92.05	gold quality
kidney epithelium	UBERON:0004819	91.96	silver quality
right frontal lobe	UBERON:0002810	91.94	gold quality
cerebellum	UBERON:0002037	91.92	gold quality
endocervix	UBERON:0000458	91.82	gold quality
ectocervix	UBERON:0012249	91.76	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.76	gold quality
mucosa of transverse colon	UBERON:0004991	91.73	gold quality
anterior cingulate cortex	UBERON:0009835	91.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.57
E-GEOD-124858	no	14.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting HDGFL2, 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-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-4781-3P	95.78	65.66	572
HSA-MIR-6750-5P	93.94	66.68	797
HSA-MIR-6822-5P	93.94	66.34	812

Literature-anchored findings (GeneRIF, showing 7)

• Here, we show that recombinant HDGF2 host cell factor efficiently reconstitutes the in vitro activity of HIV-1 preintegration complexes. (PMID:16337983)
• Authors show that HRP-2 functions as a co-factor of HIV-1 IN in LEDGF/p75-depleted cells. (PMID:23046603)
• HRP-2 is frequently overexpressed in human hepatocellular carcinoma tissues at mRNA and protein levels. HRP-2 can promote hepatocellular carcinoma cells growth in vitro and xenograft tumors in vivo. (PMID:25689719)
• HDGFRP2 promotes DNA repair by homologous recombination. (PMID:26721387)
• LEDGF and HDGF2 colocalize with Histone H3 lysine 36 methylation 2/3 at genomic regions containing active genes. (PMID:31616795)
• Unlike Its Paralog LEDGF/p75, HRP-2 Is Dispensable for MLL-R Leukemogenesis but Important for Leukemic Cell Survival. (PMID:33477970)
• Epigenomic reprogramming via HRP2-MINA dictates response to proteasome inhibitors in multiple myeloma with t(4;14) translocation. (PMID:35166240)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	hdgfl2	ENSDARG00000019530
mus_musculus	Hdgfl2	ENSMUSG00000002833

Paralogs (4): HDGFL1 (ENSG00000112273), HDGF (ENSG00000143321), PSIP1 (ENSG00000164985), HDGFL3 (ENSG00000166503)

Protein

Protein identifiers

Hepatoma-derived growth factor-related protein 2 — Q7Z4V5 (reviewed: Q7Z4V5)

Alternative names: Hepatoma-derived growth factor 2

All UniProt accessions (9): A0A087WT54, A0A087WX58, A0A087WZ99, Q7Z4V5, K7EJP7, K7EPS6, K7EQ06, K7ERA4, M0R0J3

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an epigenetic regulator of myogenesis in cooperation with DPF3a (isoform 2 of DPF3/BAF45C). Associates with the BAF complex via its interaction with DPF3a and HDGFL2-DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of SMARCA4/BRG1/BAF190A (ATPase subunit of the BAF complex) to myogenic gene promoters. Promotes the repair of DNA double-strand breaks (DSBs) through the homologous recombination pathway by facilitating the recruitment of the DNA endonuclease RBBP8 to the DSBs. Preferentially binds to chromatin regions marked by H3K9me3, H3K27me3 and H3K36me2. Involved in cellular growth control, through the regulation of cyclin D1 expression.

Subunit / interactions. Interacts with HDGF. Interacts with trimethylated ‘Lys-36’ of histone H3 (H3K36me3). Interacts with trimethylated ‘Lys-79’ of histone H3 (H3K79me3), but has higher affinity for H3K36me3. Interacts with IWS1. Interacts with H2AX, POGZ, RBBP8 and CBX1. Interacts with histones H3K9me3, H3K27me3 and H3K36me2. Interacts with DPF3a (isoform 2 of DPF3/BAF45C). Interacts with SMARCA4/BRG1/BAF190A, SMARCC1/BAF155 and SMARCD1/BAF60A in a DPF3a-dependent manner. Interacts with MPHOSPH8.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Widely expressed. High expression is found in heart, skeletal muscle, ovary and testis. Overexpression is frequently observed in hepatocellular carcinoma samples.

Similarity. Belongs to the HDGF family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q7Z4V5-1	1	yes
Q7Z4V5-2	2
Q7Z4V5-3	3
Q7Z4V5-4	4

RefSeq proteins (3): NP_001001520, NP_001335098, NP_116020 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000313	PWWP_dom	Domain
IPR021567	LEDGF_IBD	Domain
IPR035441	TFIIS/LEDGF_dom_sf	Homologous_superfamily
IPR036218	HIVI-bd_sf	Homologous_superfamily

Pfam: PF00855, PF11467

UniProt features (65 total): modified residue 25, compositionally biased region 12, helix 9, strand 6, region of interest 3, splice variant 2, mutagenesis site 2, turn 2, chain 1, domain 1, cross-link 1, coiled-coil region 1

Structure

Experimental structures (PDB)

87 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9I7A	X-RAY DIFFRACTION	1.05
9I7I	X-RAY DIFFRACTION	1.4
7HGR	X-RAY DIFFRACTION	1.41
9I7B	X-RAY DIFFRACTION	1.41
7HGO	X-RAY DIFFRACTION	1.44
7HG3	X-RAY DIFFRACTION	1.45
7HGV	X-RAY DIFFRACTION	1.48
7HH4	X-RAY DIFFRACTION	1.49
7HHG	X-RAY DIFFRACTION	1.5
7HGC	X-RAY DIFFRACTION	1.51
7HGS	X-RAY DIFFRACTION	1.51
7HG6	X-RAY DIFFRACTION	1.52
7HGB	X-RAY DIFFRACTION	1.52
7HH1	X-RAY DIFFRACTION	1.53
7HH9	X-RAY DIFFRACTION	1.54
9I7H	X-RAY DIFFRACTION	1.54
7HGF	X-RAY DIFFRACTION	1.55
7HGN	X-RAY DIFFRACTION	1.55
8Z6O	X-RAY DIFFRACTION	1.55
9GRV	X-RAY DIFFRACTION	1.55
9I7C	X-RAY DIFFRACTION	1.55
7HG4	X-RAY DIFFRACTION	1.57
7HG5	X-RAY DIFFRACTION	1.57
7HGA	X-RAY DIFFRACTION	1.57
7HGT	X-RAY DIFFRACTION	1.57
7HGX	X-RAY DIFFRACTION	1.57
7HHD	X-RAY DIFFRACTION	1.57
7HG0	X-RAY DIFFRACTION	1.58
7HG9	X-RAY DIFFRACTION	1.58
9I7E	X-RAY DIFFRACTION	1.58

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z4V5-F1	61.16	0.21

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 (26): 114, 137, 165, 230, 232, 234, 240, 266, 305, 366, 369, 370, 395, 396, 397, 399, 454, 458, 490, 625 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
21	loss of interaction with histone h3k36me2.
527–528	loss of interaction with smarca4, smarcc1, smarcd1 and dpf3/baf45c isoform 2.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 87 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, GOBP_GROWTH, GOBP_REGENERATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_CELL_GROWTH, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE, GOBP_TISSUE_REGENERATION, GOBP_POSITIVE_REGULATION_OF_DNA_REPAIR, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_POSITIVE_REGULATION_OF_GROWTH

GO Biological Process (10): DNA repair (GO:0006281), DNA recombination (GO:0006310), chromatin remodeling (GO:0006338), muscle organ development (GO:0007517), positive regulation of cell growth (GO:0030307), muscle cell differentiation (GO:0042692), skeletal muscle tissue regeneration (GO:0043403), DNA repair-dependent chromatin remodeling (GO:0140861), positive regulation of double-strand break repair via homologous recombination (GO:1905168), DNA damage response (GO:0006974)

GO Molecular Function (4): histone H3K27me3 reader activity (GO:0061628), histone H3K9me2/3 reader activity (GO:0062072), histone reader activity (GO:0140566), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	2
DNA damage response	2
muscle structure development	2
histone H3 reader activity	2
chromatin organization	1
animal organ development	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
cell differentiation	1
tissue regeneration	1
chromatin remodeling	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
positive regulation of DNA recombination	1
positive regulation of double-strand break repair	1
cellular response to stress	1
nucleosome	1
histone binding	1
chromatin-protein adaptor activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

892 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HDGFL2	IWS1	Q96ST2	499
HDGFL2	H3-3A	P06351	491
HDGFL2	CDCA7L	Q96GN5	447
HDGFL2	H4C7	Q99525	441
HDGFL2	H4C16	P02304	439
HDGFL2	BRPF1	P55201	436
HDGFL2	WFIKKN2	Q8TEU8	366
HDGFL2	VSTM2L	Q96N03	358
HDGFL2	MORF4L1	Q9UBU8	346
HDGFL2	FBRSL1	Q9HCM7	344
HDGFL2	POGZ	Q7Z3K3	329
HDGFL2	BANF2	Q9H503	326
HDGFL2	TOX4	O94842	313
HDGFL2	COPG1	Q9Y678	312
HDGFL2	TCEA1	P23193	310

IntAct

91 interactions, top by confidence:

A	B	Type	Score
CSNK2B	NMT2	psi-mi:“MI:0914”(association)	0.660
CSNK2A2	PES1	psi-mi:“MI:0914”(association)	0.640
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530
TSR1	RPSA	psi-mi:“MI:0914”(association)	0.530
FKBP11	ANKRD13D	psi-mi:“MI:0914”(association)	0.530
TERF2	HDGFL2	psi-mi:“MI:0915”(physical association)	0.510
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
HDGFL2	PDIA4	psi-mi:“MI:0915”(physical association)	0.400
HDGFL2	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
HDGFL2	SNRNP40	psi-mi:“MI:0915”(physical association)	0.400
HDGFL2	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
HDGFL2	TERF1	psi-mi:“MI:0915”(physical association)	0.370
HDGFL2	AGTR1	psi-mi:“MI:0915”(physical association)	0.370
HDGFL2	HTR2B	psi-mi:“MI:0915”(physical association)	0.370
HDGFL2	HTR6	psi-mi:“MI:0915”(physical association)	0.370
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Cbx1		psi-mi:“MI:0914”(association)	0.350
Rprd1b	POLR2B	psi-mi:“MI:0914”(association)	0.350
MYO1C	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Chek1	PKD2	psi-mi:“MI:0914”(association)	0.350
TIGD6	ZRANB2	psi-mi:“MI:0914”(association)	0.350
CHAMP1	GTPBP1	psi-mi:“MI:0914”(association)	0.350
Rrbp1	PIPSL	psi-mi:“MI:0914”(association)	0.350
Junb	RGPD3	psi-mi:“MI:0914”(association)	0.350
XRCC3	DERL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (242): HDGFRP2 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS)

ESM2 similar proteins: A2A6A1, B0BN49, B0QZF7, D2H526, E1BB50, E9PYH6, E9Q4F7, E9Q6J5, F1Q8W0, O15047, O88453, P30414, P30415, Q01538, Q14AX6, Q17QQ9, Q27450, Q3KPW4, Q3UMU9, Q4V8I5, Q505I5, Q5BKY9, Q5SW79, Q5VZP5, Q62417, Q66648, Q66PJ3, Q6A065, Q6P9P0, Q6UB99, Q7TQC7, Q7Z4V5, Q80U49, Q86VM9, Q8BYK8, Q8C5W0, Q8CFC2, Q8NEY8, Q8R0F5, Q8R2M2

Diamond homologs: A4FUF0, F4I907, F4K4D6, O75475, P51858, P51859, Q175F8, Q29NG1, Q32N87, Q3UMU9, Q49A26, Q562D5, Q5R7T2, Q5RKH0, Q5RKN4, Q5XXA9, Q5ZLS7, Q66T72, Q6K431, Q6P2L6, Q6P4K1, Q7Q161, Q7Z4V5, Q812D1, Q8MJG1, Q8MT36, Q8T079, Q8VHK7, Q922P9, Q923W4, Q925G1, Q99JF8, Q9BZ95, Q9FNE4, Q9JMG7, Q9LEY4, Q9LSV0, Q9LYZ0, Q9SF36, Q9SZE1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 118 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
Transcription of the HIV genome	6	14.4×	8e-04
Late Phase of HIV Life Cycle	6	14.0×	8e-04
HIV Life Cycle	6	13.4×	8e-04
Signaling by BRAF and RAF1 fusions	5	11.8×	3e-03
Inhibition of DNA recombination at telomere	5	11.7×	3e-03
RNA Polymerase II Pre-transcription Events	6	11.5×	1e-03
HIV Infection	6	9.9×	2e-03
Meiotic synapsis	5	9.8×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	5	20.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	7
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
58787	GRCh38/hg38 19p13.3(chr19:233565-4699472)x3	Pathogenic
59082	GRCh38/hg38 19p13.3-13.2(chr19:1972245-9648879)x3	Pathogenic

SpliceAI

2469 predictions. Top by Δscore:

Variant	Effect	Δscore
19:4472388:C:G	donor_gain	1.0000
19:4472421:GG:G	donor_gain	1.0000
19:4472422:G:GT	donor_gain	1.0000
19:4475347:GAAAC:G	donor_gain	1.0000
19:4475348:AAAC:A	donor_gain	1.0000
19:4475349:AAC:A	donor_gain	1.0000
19:4475350:AC:A	donor_gain	1.0000
19:4475350:ACG:A	donor_loss	1.0000
19:4475351:CGTA:C	donor_loss	1.0000
19:4475352:G:GG	donor_gain	1.0000
19:4475353:T:A	donor_loss	1.0000
19:4475441:CCA:C	acceptor_loss	1.0000
19:4475442:CAGA:C	acceptor_loss	1.0000
19:4475443:A:AG	acceptor_gain	1.0000
19:4475443:A:G	acceptor_loss	1.0000
19:4475444:G:GA	acceptor_gain	1.0000
19:4475444:GA:G	acceptor_gain	1.0000
19:4475444:GAGC:G	acceptor_gain	1.0000
19:4475444:GAGCC:G	acceptor_gain	1.0000
19:4475579:CTCCG:C	donor_gain	1.0000
19:4475580:TCCG:T	donor_gain	1.0000
19:4475581:CCG:C	donor_gain	1.0000
19:4475582:CG:C	donor_gain	1.0000
19:4475582:CGG:C	donor_loss	1.0000
19:4475583:GG:G	donor_gain	1.0000
19:4475584:G:GG	donor_gain	1.0000
19:4475584:GTGA:G	donor_loss	1.0000
19:4475585:T:A	donor_loss	1.0000
19:4488671:CACA:C	acceptor_loss	1.0000
19:4488673:CAG:C	acceptor_loss	1.0000

AlphaMissense

4395 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:4472382:T:A	V11E	1.000
19:4472384:T:A	F12I	1.000
19:4472384:T:C	F12L	1.000
19:4472384:T:G	F12V	1.000
19:4472385:T:C	F12S	1.000
19:4472385:T:G	F12C	1.000
19:4472386:C:A	F12L	1.000
19:4472386:C:G	F12L	1.000
19:4472388:C:A	A13D	1.000
19:4472390:A:G	K14E	1.000
19:4472392:G:C	K14N	1.000
19:4472392:G:T	K14N	1.000
19:4472394:T:A	M15K	1.000
19:4472394:T:C	M15T	1.000
19:4472396:A:G	K16E	1.000
19:4472397:A:T	K16M	1.000
19:4472398:G:C	K16N	1.000
19:4472398:G:T	K16N	1.000
19:4472399:G:A	G17S	1.000
19:4472399:G:C	G17R	1.000
19:4472399:G:T	G17C	1.000
19:4472400:G:A	G17D	1.000
19:4472400:G:T	G17V	1.000
19:4472402:T:A	Y18N	1.000
19:4472402:T:C	Y18H	1.000
19:4472402:T:G	Y18D	1.000
19:4472403:A:G	Y18C	1.000
19:4472406:C:A	P19H	1.000
19:4472408:C:G	H20D	1.000
19:4472411:T:A	W21R	1.000

dbSNP variants (sampled 300 via entrez): RS1000015291 (19:4484526 T>G), RS1000044027 (19:4471107 C>T), RS1000184050 (19:4478798 C>T), RS1000243937 (19:4472246 C>G,T), RS1000265299 (19:4495145 T>C), RS1000298425 (19:4486028 G>A), RS1000351696 (19:4485706 C>T), RS1000361826 (19:4502295 G>A), RS1000492512 (19:4478536 T>C,G), RS1000576508 (19:4473873 T>C), RS1000629146 (19:4487032 C>A,T), RS1000653313 (19:4473509 C>T), RS1000711823 (19:4474082 G>A), RS1000918027 (19:4480166 G>A), RS1000979604 (19:4499400 C>T)

Disease associations

OMIM: gene MIM:617884 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST004602_260	Mean corpuscular volume	3.000000e-81
GCST004605_26	Mean corpuscular hemoglobin concentration	7.000000e-34
GCST004611_145	High light scatter reticulocyte count	8.000000e-17
GCST004612_92	High light scatter reticulocyte percentage of red cells	1.000000e-12
GCST004615_120	Hemoglobin concentration	3.000000e-13
GCST004628_33	Immature fraction of reticulocytes	2.000000e-68
GCST004630_55	Mean corpuscular hemoglobin	4.000000e-111
GCST005993_19	Mean corpuscular hemoglobin	1.000000e-16
GCST006011_57	Mean corpuscular volume	1.000000e-15
GCST006612_120	LDL cholesterol	5.000000e-08
GCST007327_162	Smoking status (ever vs never smokers)	6.000000e-11
GCST007603_6	Smoking initiation	9.000000e-09
GCST008810_1	Smoking initiation (ever regular vs never regular)	1.000000e-08
GCST010083_97	Hemoglobin levels	9.000000e-38
GCST90002383_97	Hematocrit	4.000000e-09
GCST90002384_445	Hemoglobin	9.000000e-31
GCST90002385_306	High light scatter reticulocyte count	4.000000e-18
GCST90002386_55	High light scatter reticulocyte percentage of red cells	1.000000e-12
GCST90002387_36	Immature fraction of reticulocytes	2.000000e-160
GCST90002390_515	Mean corpuscular hemoglobin	1.000000e-220
GCST90002391_102	Mean corpuscular hemoglobin concentration	4.000000e-87
GCST90002392_55	Mean corpuscular volume	2.000000e-142
GCST90002400_263	Plateletcrit	2.000000e-11
GCST90002402_611	Platelet count	6.000000e-13
GCST90002403_274	Red blood cell count	1.000000e-16
GCST90020025_1481	Waist-to-hip ratio adjusted for BMI	5.000000e-10
GCST90020025_1482	Waist-to-hip ratio adjusted for BMI	7.000000e-10
GCST90020027_191	Waist-hip index	6.000000e-10
GCST90020027_192	Waist-hip index	2.000000e-10
GCST90020028_1641	Hip circumference adjusted for BMI	5.000000e-08

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007986	reticulocyte count
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004318	smoking behavior
EFO:0005670	smoking initiation
EFO:0004348	hematocrit
EFO:0007985	platelet crit
EFO:0004309	platelet count
EFO:0004305	erythrocyte count
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523364 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, increases expression	3
sodium arsenite	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
tetrabromobisphenol A	increases expression	1
cupric chloride	increases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
jinfukang	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Caffeine	affects phosphorylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects expression, affects response to substance	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Thiram	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4377344	Binding	Binding affinity to HDGF2 (unknown origin) assessed as induction of thermal shifts at 200 uM measured for 25 mins by SYPRO orange dye thermal shift assay	Discovery of a Potent and Selective Fragment-like Inhibitor of Methyllysine Reader Protein Spindlin 1 (SPIN1). — J Med Chem

Clinical trials (associated diseases)

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