ZFPM1

Summary

ZFPM1 (zinc finger protein, FOG family member 1, HGNC:19762) is a protein-coding gene on chromosome 16q24.2, encoding Zinc finger protein ZFPM1 (Q8IX07). Transcription regulator that plays an essential role in erythroid and megakaryocytic cell differentiation.

Enables RNA polymerase II-specific DNA-binding transcription factor binding activity and transcription corepressor activity. Involved in platelet formation; regulation of definitive erythrocyte differentiation; and regulation of gene expression. Part of transcription repressor complex.

Source: NCBI Gene 161882 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Limited, ClinGen)
• GWAS associations: 66
• Clinical variants (ClinVar): 326 total — 3 pathogenic
• Transcription factor: yes — 20 downstream targets (CollecTRI)
• MANE Select transcript: NM_153813

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19762
Approved symbol	ZFPM1
Name	zinc finger protein, FOG family member 1
Location	16q24.2
Locus type	gene with protein product
Status	Approved
Aliases	PRDM18, FOG1, FOG, ZNF89A
Ensembl gene	ENSG00000179588
Ensembl biotype	protein_coding
OMIM	601950
Entrez	161882

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000319555, ENST00000562417, ENST00000562437, ENST00000563351, ENST00000569086

RefSeq mRNA: 1 — MANE Select: NM_153813 NM_153813

CCDS: CCDS32502

Canonical transcript exons

ENST00000319555 — 10 exons

Exon	Start	End
ENSE00001220600	88532789	88532935
ENSE00001220608	88532614	88532709
ENSE00001220614	88532002	88532235
ENSE00001220620	88528032	88528238
ENSE00001220625	88526814	88526916
ENSE00001220642	88453280	88453678
ENSE00001220670	88533148	88537031
ENSE00003501706	88485939	88486043
ENSE00003733119	88514387	88514520
ENSE00003745807	88489031	88489153

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 93.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5868 / max 362.0980, expressed in 1694 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155527	14.7201	1685
155528	0.8667	284

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	93.91	silver quality
ileal mucosa	UBERON:0000331	91.11	gold quality
nasal cavity epithelium	UBERON:0005384	90.12	silver quality
kidney epithelium	UBERON:0004819	89.09	silver quality
pylorus	UBERON:0001166	87.06	gold quality
cardia of stomach	UBERON:0001162	86.59	silver quality
cerebellar vermis	UBERON:0004720	85.11	gold quality
parotid gland	UBERON:0001831	84.91	silver quality
ventral tegmental area	UBERON:0002691	84.50	silver quality
subthalamic nucleus	UBERON:0001906	83.76	silver quality
lateral globus pallidus	UBERON:0002476	83.60	silver quality
vena cava	UBERON:0004087	83.31	silver quality
jejunal mucosa	UBERON:0000399	83.16	gold quality
jejunum	UBERON:0002115	82.99	gold quality
mucosa of paranasal sinus	UBERON:0005030	82.75	gold quality
dorsal plus ventral thalamus	UBERON:0001897	82.56	silver quality
inferior vagus X ganglion	UBERON:0005363	82.08	silver quality
biceps brachii	UBERON:0001507	81.97	silver quality
heart right ventricle	UBERON:0002080	81.97	silver quality
epithelium of mammary gland	UBERON:0003244	81.63	silver quality
mammary duct	UBERON:0001765	81.58	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	81.49	silver quality
parietal lobe	UBERON:0001872	81.48	gold quality
postcentral gyrus	UBERON:0002581	81.41	gold quality
superior surface of tongue	UBERON:0007371	81.40	silver quality
granulocyte	CL:0000094	81.34	gold quality
thymus	UBERON:0002370	81.25	silver quality
substantia nigra pars reticulata	UBERON:0001966	81.16	gold quality
medulla oblongata	UBERON:0001896	81.01	silver quality
trabecular bone tissue	UBERON:0002483	81.01	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.14

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

20 targets.

Target	Regulation
ADAM2
CEL
CREBBP
DLD
FCER1G
FOXN1
GATA2	Repression
HBB
HBG1
IFNG	Unknown
IL5	Repression
ITGA2B
MBP
MED1
NELFE
NFE2	Activation
SPG21
SPTA1
TAC1
TACC3

Upstream regulators (CollecTRI, top): CEBPG, GATA1, SPI1

miRNA regulators (miRDB)

17 targeting ZFPM1, 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-302E	99.96	70.74	2669
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-4477A	98.83	69.75	2952

Literature-anchored findings (GeneRIF, showing 18)

• X-linked thrombocytopenia with thalassemia from a mutation in the amino finger of GATA-1 affects DNA binding but does not affect FOG-1 interaction.(FOG1, cofactor of GATA1) (PMID:12200364)
• Erythroid and megakaryocytic lineage differentiation and maturation are regulated via cooperation between transcription factor GATA1 and its essential cofactor FOG1. It depends on the binding of FOG1 to the N-terminalfinger of GATA1. (PMID:12483298)
• 3D structure of a complex comprising the interaction domains of FOG1 and GATA1 reveals how zinc fingers can act as protein recognition motifs and provides a molecular explanation for how GATA-1 mutations contribute to distinct, related genetic diseases. (PMID:15644435)
• Megakaryocytes from idiopathic myelofibrosis patients have reduced GATA-1 content, possibly contributing to disease pathogenesis as in the GATA-1(low) mice. (PMID:16127162)
• Data verified the function of Zfpm-1 during erythropoietic differentiation. (PMID:17207461)
• FOG-1 inhibits mast-cell differentiation in a differentiation stage-dependent manner, and its effects are produced via different molecular mechanisms. (PMID:18063754)
• two novel mechanisms for the regulation of GATA1 interaction with FOG1-dependent protein complexes through the production of two translational isoforms with differential interaction profiles and independent nuclear localization controls. (PMID:19654328)
• Anagrelide suppresses megakaryocytopoiesis by reducing the expression levels of GATA-1 and FOG-1 via a PDEIII-independent mechanism that is differentiation context-specific and does not involve inhibition of MPL-mediated early signal transduction events (PMID:20586925)
• The FOG-1 peptide contacts a negatively charged binding pocket on top of the RbAp48 beta-propeller that is distinct from the binding surface used by RpAp48 to contact histone H4 (PMID:21047798)
• ZFPM1 that facilitates human Th1 differentiation via the downregulation of IL-4 is a potential target for the treatment of allergic diseases. (PMID:21646796)
• FOG1, FOG2 and GATA-6 modulate the transcriptional up-regulation of HAMP in hepatocytes during inflammation. (PMID:24179092)
• FOG1 is a member of the PR domain containing, zinc finger protein family of transcriptional regulators. (PMID:25162672)
• Our results reveal that the protein structure does not affect ligand binding, and the top three TCM candidates Bittersweet alkaloid II, Eicosandioic acid, and Perivine might resolve the instability of the RbAp48-FOG1 complex (PMID:25165715)
• GAB2, GSPT1, TFDP2 and ZFPM1 are four new susceptibility loci for testicular germ cell tumor. (PMID:26503584)
• Forced FOG1 protein expression in K562 erythroleukemia cells induced the expression of SLC4A1 protein, but repressed that of transcription factor PU.1. (PMID:28216155)
• Long Noncoding RNA ZFPM2-AS1 Knockdown Restrains the Development of Retinoblastoma by Modulating the MicroRNA-515/HOXA1/Wnt/beta-Catenin Axis. (PMID:32561925)
• The upregulation of Gata transcription factors family and FOG-1 in expanded and differentiated cord blood-derived CD34[+] hematopoietic stem cells to megakaryocyte lineage during co-culture with cord blood mesenchymal stem cells. (PMID:35690555)
• PI3K/HSCB axis facilitates FOG1 nuclear translocation to promote erythropoiesis and megakaryopoiesis. (PMID:38757931)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	zfpm1	ENSDARG00000041572
mus_musculus	Zfpm1	ENSMUSG00000049577
rattus_norvegicus	Zfpm1	ENSRNOG00000043077
drosophila_melanogaster	ush	FBGN0003963

Paralogs (1): ZFPM2 (ENSG00000169946)

Protein

Protein identifiers

Zinc finger protein ZFPM1 — Q8IX07 (reviewed: Q8IX07)

Alternative names: Friend of GATA protein 1, Zinc finger protein 89A, Zinc finger protein multitype 1

All UniProt accessions (4): A0A087WWQ0, A0A087WZP1, A0A087X1H8, Q8IX07

UniProt curated annotations — full annotation on UniProt →

Function. Transcription regulator that plays an essential role in erythroid and megakaryocytic cell differentiation. Essential cofactor that acts via the formation of a heterodimer with transcription factors of the GATA family GATA1, GATA2 and GATA3. Such heterodimer can both activate or repress transcriptional activity, depending on the cell and promoter context. The heterodimer formed with GATA proteins is essential to activate expression of genes such as NFE2, ITGA2B, alpha- and beta-globin, while it represses expression of KLF1. May be involved in regulation of some genes in gonads. May also be involved in cardiac development, in a non-redundant way with ZFPM2/FOG2.

Subunit / interactions. Interacts with corepressor CTBP2; this interaction is however not essential for corepressor activity. Interacts with the N-terminal zinc-finger of GATA1, GATA2 and probably GATA3.

Subcellular location. Nucleus.

Tissue specificity. Mainly expressed in hematopoietic tissues. Also expressed in adult cerebellum, stomach, lymph node, liver and pancreas. Expressed in fetal heart, liver and spleen.

Domain organisation. The CCHC FOG-type zinc fingers 1, 2, 3 and 5 directly bind to GATA-type zinc fingers. The Tyr residue adjacent to the last Cys of the CCHC FOG-type zinc finger is essential for the interaction with GATA-type zinc fingers.

Similarity. Belongs to the FOG (Friend of GATA) family.

RefSeq proteins (1): NP_722520* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR034731	Znf_CCHC_FOG	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR039746	FOG	Family
IPR049361	ZFPM1/2_PR	Domain
IPR059121	CCHC_ZFPM2-like	Domain

Pfam: PF00096, PF21182, PF25445

UniProt features (67 total): binding site 20, modified residue 13, compositionally biased region 11, region of interest 10, zinc finger region 9, sequence conflict 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2XU7	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IX07-F1	56.32	0.01

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (20): 243; 246; 259; 264; 579; 582; 595; 600; 685; 688; 701; 706 …

Post-translational modifications (13): 84, 128, 272, 384, 491, 494, 638, 671, 786, 901, 909, 914, 935

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 251 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, PID_HDAC_CLASSI_PATHWAY, GOBP_EMBRYONIC_HEMOPOIESIS, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, PEREZ_TP63_TARGETS

GO Biological Process (34): negative regulation of transcription by RNA polymerase II (GO:0000122), T-helper cell lineage commitment (GO:0002295), outflow tract morphogenesis (GO:0003151), atrioventricular valve morphogenesis (GO:0003181), mitral valve formation (GO:0003192), tricuspid valve formation (GO:0003195), heart development (GO:0007507), regulation of definitive erythrocyte differentiation (GO:0010724), erythrocyte differentiation (GO:0030218), megakaryocyte differentiation (GO:0030219), platelet formation (GO:0030220), granulocyte differentiation (GO:0030851), regulation of chemokine production (GO:0032642), negative regulation of interleukin-4 production (GO:0032713), positive regulation of type II interferon production (GO:0032729), embryonic hemopoiesis (GO:0035162), megakaryocyte development (GO:0035855), positive regulation of transcription by RNA polymerase II (GO:0045944), cardiac muscle tissue morphogenesis (GO:0055008), definitive erythrocyte differentiation (GO:0060318), primitive erythrocyte differentiation (GO:0060319), negative regulation of mast cell differentiation (GO:0060377), ventricular septum morphogenesis (GO:0060412), atrial septum morphogenesis (GO:0060413), regulation of cytokine production (GO:0001817), immune system process (GO:0002376), leukocyte differentiation (GO:0002521), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of macromolecule biosynthetic process (GO:0010557), myeloid cell differentiation (GO:0030099), regulation of myeloid cell differentiation (GO:0045637), anatomical structure formation involved in morphogenesis (GO:0048646), homeostasis of number of cells (GO:0048872), negative regulation of multicellular organismal process (GO:0051241)

GO Molecular Function (6): DNA binding (GO:0003677), transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), transcription repressor complex (GO:0017053)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Transcriptional regulation by RUNX1	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
myeloid cell differentiation	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
heart morphogenesis	2
atrioventricular valve formation	2
cellular anatomical structure	2
T-helper cell differentiation	1
CD4-positive, alpha-beta T cell lineage commitment	1
anatomical structure morphogenesis	1
atrioventricular valve development	1
heart valve morphogenesis	1
mitral valve morphogenesis	1
tricuspid valve morphogenesis	1
animal organ development	1
circulatory system development	1
regulation of erythrocyte differentiation	1
definitive erythrocyte differentiation	1
erythrocyte homeostasis	1
platelet morphogenesis	1
anatomical structure formation involved in morphogenesis	1
myeloid leukocyte differentiation	1
regulation of cytokine production	1
chemokine production	1
negative regulation of cytokine production	1
interleukin-4 production	1
regulation of interleukin-4 production	1
positive regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
hemopoiesis	1
embryonic organ development	1
megakaryocyte differentiation	1
myeloid cell development	1
positive regulation of DNA-templated transcription	1
cardiac muscle tissue development	1
muscle tissue morphogenesis	1
erythrocyte differentiation	1
definitive hemopoiesis	1
nucleic acid binding	1

Protein interactions and networks

STRING

1238 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZFPM1	GATA1	P15976	999
ZFPM1	GATA2	P23769	980
ZFPM1	LMO2	P25791	972
ZFPM1	LDB1	Q86U70	938
ZFPM1	LDB2	O43679	900
ZFPM1	KLF1	Q13351	875
ZFPM1	HDAC1	Q13547	871
ZFPM1	TAL1	P17542	813
ZFPM1	GATA4	P43694	790
ZFPM1	CTBP1	Q13363	788
ZFPM1	BCL11A	Q9H165	765
ZFPM1	CHD4	Q14839	756
ZFPM1	NFE2	Q16621	738
ZFPM1	SPI1	P17947	725
ZFPM1	CTBP2	P56545	645

IntAct

19 interactions, top by confidence:

A	B	Type	Score
ZFPM1	RBBP4	psi-mi:“MI:0407”(direct interaction)	0.800
RBBP4	ZFPM1	psi-mi:“MI:0407”(direct interaction)	0.800
ERP44	MEX3A	psi-mi:“MI:0914”(association)	0.530
DEFA6	EXTL3	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
GSK3B	ZFPM1	psi-mi:“MI:0915”(physical association)	0.510
ZFPM1	GSK3B	psi-mi:“MI:0915”(physical association)	0.510
GATA1	ZFPM1	psi-mi:“MI:0915”(physical association)	0.400
CTBP2	ZFPM1	psi-mi:“MI:0915”(physical association)	0.370
GATA2	IMPDH1	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
RBBP4	PHF20L1	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): ZFPM1 (Affinity Capture-MS), ZFPM1 (Affinity Capture-MS), ZFPM1 (Affinity Capture-MS), ZFPM1 (Affinity Capture-RNA), ZFPM1 (Affinity Capture-MS), ZFPM1 (Affinity Capture-MS), ZFPM1 (Affinity Capture-MS), ZFPM1 (Affinity Capture-MS), ZFPM1 (Affinity Capture-Western), ZFPM1 (Affinity Capture-MS), GATA1 (Affinity Capture-Western), ZFPM1 (Affinity Capture-Western), Rb1 (Affinity Capture-Western), ZFPM1 (Affinity Capture-RNA), ZFPM1 (Protein-peptide)

ESM2 similar proteins: A0JNJ4, A2APT9, A6NEL2, A6NP61, B1ASB6, B1WBS3, B2RXF5, F6WEQ6, O15015, O43918, O88282, O88286, O95785, P98168, P98169, Q2M3G4, Q2MHN3, Q2QGD7, Q3U1J1, Q3U381, Q497V6, Q5SW24, Q5SXM2, Q6YND2, Q6ZMQ8, Q6ZMY3, Q7TN08, Q7TSX9, Q80SU3, Q80YE4, Q811H0, Q8BG26, Q8BZW2, Q8C8V1, Q8IX07, Q8IY92, Q8N143, Q8N1G0, Q8NC74, Q8TBE0

Diamond homologs: A1L2U9, A2A884, A2ANX9, A7Y7X5, B0X9H6, B0YDH7, B1WAZ8, B1WBU4, O35615, O62836, O77459, P08048, P10925, P15822, P17010, P17012, P20662, P31505, P31629, P60319, P78871, P80944, Q00900, Q01611, Q02031, Q03172, Q0IH98, Q0VCJ6, Q292R5, Q29419, Q3UHF7, Q52V16, Q5JPB2, Q5T1R4, Q6B4Z5, Q7JM44, Q811F1, Q86UZ6, Q8BID6, Q8CII0

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
GATA1	“up-regulates activity”	ZFPM1	binding
ZFPM1	“down-regulates quantity by repression”	GATA2	“transcriptional regulation”
ZFPM1	“up-regulates activity”	Megakaryocyte_differentiation
ZFPM1	“up-regulates activity”	Erythrocyte_differentiation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	284
Likely benign	20
Benign	4

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
267476	Single allele	Pathogenic
3243614	NC_000016.9:g.(?88500082)(88520238_?)del	Pathogenic
560033	Single allele	Pathogenic

SpliceAI

3395 predictions. Top by Δscore:

Variant	Effect	Δscore
16:88486041:CAGG:C	donor_loss	1.0000
16:88486042:AGGTG:A	donor_loss	1.0000
16:88486043:GGT:G	donor_loss	1.0000
16:88486044:GT:G	donor_loss	1.0000
16:88486045:T:A	donor_loss	1.0000
16:88489123:G:GT	donor_gain	1.0000
16:88526912:G:GT	donor_gain	1.0000
16:88526915:GG:G	donor_gain	1.0000
16:88526916:GG:G	donor_gain	1.0000
16:88528239:G:GG	donor_gain	1.0000
16:88532000:A:AG	acceptor_gain	1.0000
16:88532001:G:GA	acceptor_gain	1.0000
16:88532001:GAA:G	acceptor_gain	1.0000
16:88532233:GCG:G	donor_gain	1.0000
16:88532233:GCGGT:G	donor_loss	1.0000
16:88532234:CGGTG:C	donor_loss	1.0000
16:88532235:GGTGA:G	donor_loss	1.0000
16:88532236:G:GA	donor_loss	1.0000
16:88532236:G:GG	donor_gain	1.0000
16:88532237:TGAG:T	donor_loss	1.0000
16:88532707:GCG:G	donor_gain	1.0000
16:88532709:GGT:G	donor_loss	1.0000
16:88532710:GTAGG:G	donor_loss	1.0000
16:88532786:CAGGT:C	acceptor_loss	1.0000
16:88532787:A:AC	acceptor_loss	1.0000
16:88532788:G:A	acceptor_loss	1.0000
16:88532788:GGT:G	acceptor_gain	1.0000
16:88533147:GACA:G	acceptor_gain	1.0000
16:88453439:G:GT	donor_gain	0.9900
16:88453677:GC:G	donor_gain	0.9900

AlphaMissense

6430 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:88532016:T:A	C243S	1.000
16:88532016:T:C	C243R	1.000
16:88532017:G:A	C243Y	1.000
16:88532017:G:C	C243S	1.000
16:88532018:C:G	C243W	1.000
16:88532025:T:A	C246S	1.000
16:88532025:T:C	C246R	1.000
16:88532026:G:A	C246Y	1.000
16:88532026:G:C	C246S	1.000
16:88532027:T:G	C246W	1.000
16:88532056:T:C	L256P	1.000
16:88532064:C:G	H259D	1.000
16:88532081:C:G	C264W	1.000
16:88532163:T:A	C292S	1.000
16:88532163:T:C	C292R	1.000
16:88532164:G:C	C292S	1.000
16:88532165:C:G	C292W	1.000
16:88532178:T:C	C297R	1.000
16:88532190:T:C	C301R	1.000
16:88532209:T:C	L307P	1.000
16:88532215:T:A	I309N	1.000
16:88532215:T:C	I309T	1.000
16:88532215:T:G	I309S	1.000
16:88532217:C:A	H310N	1.000
16:88532217:C:G	H310D	1.000
16:88532219:C:A	H310Q	1.000
16:88532219:C:G	H310Q	1.000
16:88532625:T:C	F320L	1.000
16:88532627:C:A	F320L	1.000
16:88532627:C:G	F320L	1.000

dbSNP variants (sampled 300 via entrez): RS1000014011 (16:88518097 C>A,G,T), RS1000022964 (16:88452478 G>GC), RS1000029778 (16:88490616 C>T), RS1000030630 (16:88486234 G>A,C,T), RS1000059386 (16:88463549 C>G,T), RS1000069689 (16:88456728 G>A), RS1000099886 (16:88463230 G>A), RS1000102640 (16:88477990 T>A,G), RS1000159761 (16:88470080 A>G,T), RS1000192758 (16:88450760 C>A,T), RS1000202507 (16:88507416 T>G), RS1000221302 (16:88465423 G>A), RS1000232491 (16:88452794 A>G), RS1000251316 (16:88525133 G>A), RS1000258619 (16:88487774 A>G,T)

Disease associations

OMIM: gene MIM:601950 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital heart disease	Limited	AD

Mondo (2): 16q24.3 microdeletion syndrome (MONDO:0016838), congenital heart disease (MONDO:0005453)

Orphanet (1): 16q24.3 microdeletion syndrome (Orphanet:261250)

HPO phenotypes

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

GWAS associations

66 associations (top):

Study	Trait	p-value
GCST002926_4	Bone mineral accretion in asthma (oral corticosteroid dose interaction)	4.000000e-08
GCST003247_3	Testicular germ cell tumor	3.000000e-09
GCST003403_9	Vascular endothelial growth factor levels	1.000000e-09
GCST003479_9	Hair color	1.000000e-07
GCST004600_137	Eosinophil percentage of white cells	4.000000e-13
GCST004601_140	Red blood cell count	4.000000e-11
GCST004602_283	Mean corpuscular volume	2.000000e-09
GCST004603_243	Platelet count	9.000000e-19
GCST004604_25	Hematocrit	3.000000e-09
GCST004606_22	Eosinophil count	7.000000e-14
GCST004607_65	Plateletcrit	1.000000e-19
GCST004617_116	Eosinophil percentage of granulocytes	4.000000e-11
GCST004618_41	White blood cell count (basophil)	5.000000e-18
GCST004619_1	Reticulocyte fraction of red cells	5.000000e-09
GCST004622_41	Reticulocyte count	6.000000e-13
GCST004623_80	Neutrophil percentage of granulocytes	6.000000e-09
GCST004624_4	Sum eosinophil basophil counts	3.000000e-12
GCST004630_207	Mean corpuscular hemoglobin	8.000000e-10
GCST004631_29	Basophil percentage of white cells	1.000000e-13
GCST004634_45	Basophil percentage of granulocytes	2.000000e-12
GCST004635_34	Testicular germ cell tumor	3.000000e-09
GCST004713_34	Testicular germ cell tumor	1.000000e-07
GCST005976_23	White blood cell count (basophil)	6.000000e-14
GCST005982_10	Calcium levels	6.000000e-19
GCST005991_40	Platelet count	2.000000e-10
GCST006612_111	LDL cholesterol	2.000000e-08
GCST009150_13	Low density lipoprotein cholesterol levels	5.000000e-09
GCST010204_67	Low density lipoprotein cholesterol levels	6.000000e-09
GCST010245_95	LDL cholesterol levels	2.000000e-08
GCST010320_7	PR interval	5.000000e-11

EFO canonical traits (25, from GWAS)

EFO ID	Trait name
EFO:0007591	bone mineral accretion measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004305	erythrocyte count
EFO:0004309	platelet count
EFO:0004348	hematocrit
EFO:0004842	eosinophil count
EFO:0007985	platelet crit
EFO:0007996	eosinophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0007986	reticulocyte count
EFO:0007994	neutrophil percentage of granulocytes
EFO:0004527	mean corpuscular hemoglobin
EFO:0007992	basophil percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0004838	calcium measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004462	PR interval
EFO:0004327	electrocardiography
EFO:0004574	total cholesterol measurement
EFO:0004587	lymphocyte count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0010701	mean reticulocyte volume
EFO:0007984	platelet component distribution width
EFO:0009188	Red cell distribution width
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs56292801	MIR5189, ZFPM1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
Acetaminophen	increases expression	2
Arsenic	affects methylation, affects binding, decreases reaction	2
Benzo(a)pyrene	affects methylation, increases methylation	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases methylation	1
anagrelide	decreases reaction, increases expression	1
(+)-JQ1 compound	decreases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Caffeine	affects phosphorylation	1
Coumestrol	decreases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Sodium Selenite	increases expression	1
Thapsigargin	increases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE