ZMYM2

Summary

ZMYM2 (zinc finger MYM-type containing 2, HGNC:12989) is a protein-coding gene on chromosome 13q12.11, encoding Zinc finger MYM-type protein 2 (Q9UBW7). Involved in the negative regulation of transcription.

The protein encoded by this gene is a zinc finger protein that may act as a transcription factor. The encoded protein may be part of a BHC histone deacetylase complex. Translocation of this gene with the fibroblast growth factor receptor-1 gene (FGFR1) results in a fusion gene, which may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Several transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 7750 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 428 total — 45 pathogenic, 45 likely-pathogenic
• Phenotypes (HPO): 73
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_197968

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12989
Approved symbol	ZMYM2
Name	zinc finger MYM-type containing 2
Location	13q12.11
Locus type	gene with protein product
Status	Approved
Aliases	RAMP, FIM, MYM
Ensembl gene	ENSG00000121741
Ensembl biotype	protein_coding
OMIM	602221
Entrez	7750

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 21 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000382870, ENST00000382871, ENST00000382874, ENST00000382881, ENST00000382883, ENST00000468677, ENST00000490152, ENST00000490422, ENST00000494061, ENST00000610343, ENST00000620447, ENST00000875034, ENST00000875035, ENST00000875036, ENST00000875037, ENST00000875038, ENST00000875039, ENST00000875040, ENST00000875041, ENST00000938942, ENST00000938943, ENST00000938944, ENST00000938945, ENST00000938946, ENST00000938947, ENST00000938948, ENST00000938949, ENST00000938950

RefSeq mRNA: 11 — MANE Select: NM_197968 NM_001190964, NM_001190965, NM_001353157, NM_001353159, NM_001353161, NM_001353162, NM_001353163, NM_001353164, NM_001353165, NM_003453, NM_197968

CCDS: CCDS45016

Canonical transcript exons

ENST00000610343 — 25 exons

Exon	Start	End
ENSE00000994796	19959958	19960026
ENSE00001493682	20034254	20034404
ENSE00001701375	20031319	20031435
ENSE00001766044	20005074	20005239
ENSE00002289331	19993063	19993919
ENSE00003493325	20019547	20019618
ENSE00003594100	20027203	20027318
ENSE00003632758	20026612	20026762
ENSE00003705144	20059447	20059562
ENSE00003705601	20061053	20061224
ENSE00003706500	20082781	20083032
ENSE00003706670	20066851	20067019
ENSE00003706961	20051433	20051598
ENSE00003707483	20082016	20082130
ENSE00003708852	20052277	20052311
ENSE00003709923	20064451	20064545
ENSE00003710361	20062846	20062971
ENSE00003710456	20083656	20083776
ENSE00003710675	20036737	20036909
ENSE00003711029	20067239	20067390
ENSE00003711449	20058575	20058704
ENSE00003722766	20006374	20006586
ENSE00003724433	20002850	20003135
ENSE00003729538	19958727	19958841
ENSE00003915555	20085822	20089115

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.2573 / max 692.9407, expressed in 1796 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134290	23.2419	1772
134292	2.5504	1256
134289	2.3082	1035
134293	2.2087	1160
134291	1.4414	836
206968	1.2308	567
206969	0.6954	463
134295	0.6249	273
134287	0.4119	197
134294	0.3289	116

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.28	gold quality
oocyte	CL:0000023	97.56	gold quality
secondary oocyte	CL:0000655	97.53	gold quality
ganglionic eminence	UBERON:0004023	96.70	gold quality
buccal mucosa cell	CL:0002336	96.65	gold quality
right testis	UBERON:0004534	96.65	gold quality
calcaneal tendon	UBERON:0003701	96.47	gold quality
male germ cell	CL:0000015	96.45	gold quality
left testis	UBERON:0004533	96.42	gold quality
cortical plate	UBERON:0005343	96.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.26	gold quality
ventricular zone	UBERON:0003053	96.20	gold quality
testis	UBERON:0000473	96.16	gold quality
lower esophagus mucosa	UBERON:0035834	96.01	gold quality
adrenal tissue	UBERON:0018303	95.97	gold quality
tibia	UBERON:0000979	95.29	gold quality
embryo	UBERON:0000922	94.66	gold quality
tonsil	UBERON:0002372	94.52	gold quality
endometrium	UBERON:0001295	94.42	gold quality
mucosa of stomach	UBERON:0001199	94.31	gold quality
corpus callosum	UBERON:0002336	94.30	gold quality
right uterine tube	UBERON:0001302	94.17	gold quality
skin of abdomen	UBERON:0001416	94.01	gold quality
tongue squamous epithelium	UBERON:0006919	93.99	gold quality
adenohypophysis	UBERON:0002196	93.93	gold quality
palpebral conjunctiva	UBERON:0001812	93.90	gold quality
germinal epithelium of ovary	UBERON:0001304	93.85	gold quality
tibial nerve	UBERON:0001323	93.70	gold quality
skin of leg	UBERON:0001511	93.67	gold quality
endothelial cell	CL:0000115	93.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.07
E-MTAB-6142	no	174.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

281 targeting ZMYM2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 21)

• ZNF198/fibroblast growth factor receptor-1 has signaling function comparable with interleukin-6 cytokine receptors. (PMID:12594223)
• cell transformation mediated by ZNF198-FGFR1 requires STAT5 activation (PMID:14660670)
• SUMO-1, PML and ZNF198 colocalize to punctate structures, shown by immunocytochemistry to be PML bodies. (PMID:17027752)
• ZNF198-FGFR1 activated both the AKT and mitogen activated protein kinase (MAPK) prosurvival signaling pathways, resulting in elevated phosphorylation of the AKT target FOXO3a at T32 and BAD at S112, respectively. (PMID:17389761)
• HSPA1A is an important regulator of the stability and function of ZNF198 and its oncogenic derivative, ZNF198-FGFR1. (PMID:17471537)
• ZNF198, through its multiple protein-protein interaction interfaces, helps to maintain the intact LSD1-CoREST-HDAC1 complex on specific, non-REST-responsive promoters and may also prevent SUMO-dependent dissociation of HDAC1 (PMID:18806873)
• An important event in the process of ZNF198-FGFR1-induced T-cell leukemia. (PMID:19506298)
• ZNF198-FGFR1 is associated with phosphorylation of several proteins including SSBP2, ABL, FLJ14235, CALM and TRIM4 proteins. (PMID:19658100)
• We propose Plk1 activity down-regulates ZNF198 and SUZ12, thereby enhancing both HBV replication and pX-mediated oncogenic transformation. (PMID:21480320)
• B-lymphoblastic leukemia/lymphoma associated with t(8;13)(p11;q12)/ ZMYM2 (ZNF198)-FGFR1 (PMID:23594707)
• downregulation of SUZ12 and ZNF198 leads to epigenetic reprogramming of infected hepatocytes. Because both Plk1 and HOTAIR are elevated in many human cancers, we propose that their combined effects are involved in epigenetic reprogramming (PMID:25855382)
• Multi-SUMO binding is mediated through multi-SIM modules, and the functional importance of these interactions is demonstrated for the transcriptional corepressor ZMYM2/ZNF198 (PMID:26283374)
• In this report we described the first successful development of a model of human ZMYM2-FGFR1 driven AML in immunocompromised mice, which shows an etiology consistent with the development of the primary human disease. (PMID:27005999)
• study found that ZMYM2-FLT3 and DIAPH1-PDGFRB fusion genes are novel, cytogenetically cryptic and therapeutically targetable abnormalities in myeloproliferative neoplasms with eosinophilia, and are thus reminiscent of FIP1L1-PDGFRA positive myeloid neoplasms (PMID:28751768)
• Characterization of the zinc finger proteins ZMYM2 and ZMYM4 as novel B-MYB binding proteins. (PMID:32439918)
• The Chromatin Regulator ZMYM2 Restricts Human Pluripotent Stem Cell Growth and Is Essential for Teratoma Formation. (PMID:32559458)
• Mutations of the Transcriptional Corepressor ZMYM2 Cause Syndromic Urinary Tract Malformations. (PMID:32891193)
• Proteomic analysis identifies ZMYM2 as endogenous binding partner of TBX18 protein in 293 and A549 cells. (PMID:34935912)
• UBE2B promotes ovarian cancer growth via promoting RAD18 mediated ZMYM2 monoubiquitination and stabilization. (PMID:35313791)
• ZMYM2 is essential for methylation of germline genes and active transposons in embryonic development. (PMID:37395395)
• ZMYM2 controls human transposable element transcription through distinct co-regulatory complexes. (PMID:37934570)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zmym2	ENSDARG00000027353
mus_musculus	Zmym2	ENSMUSG00000021945
rattus_norvegicus	Zmym2	ENSRNOG00000008734

Paralogs (18): GTF2IRD1 (ENSG00000006704), ZMYM5 (ENSG00000132950), THAP12 (ENSG00000137492), ZMYM4 (ENSG00000146463), ZMYM3 (ENSG00000147130), ZMYM6 (ENSG00000163867), KIAA1958 (ENSG00000165185), GTF2IRD2B (ENSG00000174428), EPM2AIP1 (ENSG00000178567), GTF2IRD2 (ENSG00000196275), ZMYM1 (ENSG00000197056), QRICH1 (ENSG00000198218), FAM200C (ENSG00000221886), FAM200A (ENSG00000221909), SCAND3 (ENSG00000232040), ZBED5 (ENSG00000236287), FAM200B (ENSG00000237765), GTF2I (ENSG00000263001)

Protein

Protein identifiers

Zinc finger MYM-type protein 2 — Q9UBW7 (reviewed: Q9UBW7)

Alternative names: Fused in myeloproliferative disorders protein, Rearranged in atypical myeloproliferative disorder protein, Zinc finger protein 198

All UniProt accessions (2): A0A087X151, Q9UBW7

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the negative regulation of transcription.

Subunit / interactions. Can form homodimers. May be a component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST, PHF21A/BHC80, ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Interacts with FOXP1 and FOXP2.

Subcellular location. Nucleus.

Disease relevance. Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities (NECRC) [MIM:619522] An autosomal dominant disorder characterized by dysmorphic craniofacial features, mild developmental delay, mildly impaired intellectual development or learning difficulties, speech delay, and behavioral abnormalities. About half of patients have congenital anomalies of the kidney and urinary tract and/or congenital cardiac defects, including septal defects. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving ZMYM2 may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Translocation t(8;13)(p11;q12) with FGFR1. SCLL usually presents as lymphoblastic lymphoma in association with a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UBW7-1	1	yes
Q9UBW7-2	2

RefSeq proteins (11): NP_001177893, NP_001177894, NP_001340086, NP_001340088, NP_001340090, NP_001340091, NP_001340092, NP_001340093, NP_001340094, NP_003444, NP_932072* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010507	Znf_MYM	Domain
IPR011017	TRASH_dom	Domain
IPR021893	ZMYM2-like_C	Domain
IPR051284	ZnF_MYMT-QRICH1	Family
IPR057926	QRICH1_dom	Domain

Pfam: PF06467, PF12012, PF25561

UniProt features (85 total): cross-link 29, sequence variant 15, sequence conflict 12, zinc finger region 8, compositionally biased region 6, modified residue 6, region of interest 4, splice variant 3, chain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBW7-F1	61.50	0.18

Functional residue map

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

Catalytic / active sites (1): 913–914 (breakpoint for translocation to form zmym2-fgfr1)

Post-translational modifications (35): 159, 305, 838, 958, 1064, 1376, 48, 88, 98, 104, 147, 253, 297, 312, 325, 348, 366, 417, 441, 491 …

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1839117	Signaling by cytosolic FGFR1 fusion mutants
R-HSA-5655302	Signaling by FGFR1 in disease
R-HSA-9703465	Signaling by FLT3 fusion proteins
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription

MSigDB gene sets: 469 (showing top): AHRARNT_01, RNGTGGGC_UNKNOWN, E2F_Q4, E2F_Q4_01, RRAGTTGT_UNKNOWN, AAGCAAT_MIR137, LEE_NEURAL_CREST_STEM_CELL_DN, MULLIGHAN_NPM1_SIGNATURE_3_UP, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GCANCTGNY_MYOD_Q6, TTTGTAG_MIR520D, GCM_ZNF198, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, CAGCTG_AP4_Q5, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS

GO Biological Process (1): negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (4): zinc ion binding (GO:0008270), ubiquitin conjugating enzyme binding (GO:0031624), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), PML body (GO:0016605)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
FGFR1 mutant receptor activation	1
Signaling by FGFR in disease	1
FLT3 signaling in disease	1
Regulation of CDH1 Gene Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
transition metal ion binding	1
ubiquitin-like protein conjugating enzyme binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1
nuclear body	1

Protein interactions and networks

STRING

1996 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZMYM2	RCOR1	Q9UKL0	886
ZMYM2	FGFR1OP2	Q9NVK5	870
ZMYM2	FGFR1	P11362	866
ZMYM2	HDAC1	Q13547	858
ZMYM2	HMG20B	Q9P0W2	831
ZMYM2	PHF21A	Q96BD5	814
ZMYM2	GTF2I	P78347	813
ZMYM2	KDM1A	O60341	811
ZMYM2	GSE1	Q14687	753
ZMYM2	HDAC2	Q92769	720
ZMYM2	ZNF217	O75362	715
ZMYM2	PARP4	Q9UKK3	686
ZMYM2	ZMYM3	Q14202	654
ZMYM2	ZNF112	Q9UJU3	630
ZMYM2	CEP43	O95684	616

IntAct

179 interactions, top by confidence:

A	B	Type	Score
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
ARRDC1	WWP2	psi-mi:“MI:0914”(association)	0.850
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
ZMYM2	GTF2IRD1	psi-mi:“MI:0915”(physical association)	0.670
GTF2IRD1	ZMYM2	psi-mi:“MI:0915”(physical association)	0.670
GTF2IRD1	ZMYM2	psi-mi:“MI:0403”(colocalization)	0.670
GTF2IRD1	ZMYM2	psi-mi:“MI:2364”(proximity)	0.670
ZNF202	SCAND1	psi-mi:“MI:0914”(association)	0.660
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
ARRDC1	NEDD4	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
GMCL1	ZMYM2	psi-mi:“MI:0915”(physical association)	0.560
ZMYM2	IKZF3	psi-mi:“MI:0915”(physical association)	0.560
PAICS	ZMYM2	psi-mi:“MI:0915”(physical association)	0.560
ST8SIA1	POTEF	psi-mi:“MI:0914”(association)	0.530
PSG8	PEX7	psi-mi:“MI:0914”(association)	0.530
TSPYL6	NME4	psi-mi:“MI:0914”(association)	0.530
PDGFRL	ANKRD28	psi-mi:“MI:0914”(association)	0.530

BioGRID (390): ZMYM2 (Affinity Capture-MS), ZMYM2 (Co-localization), ZMYM2 (Reconstituted Complex), ZMYM2 (Affinity Capture-MS), ZMYM2 (Affinity Capture-MS), ZMYM2 (Affinity Capture-MS), ZMYM2 (Affinity Capture-MS), ZMYM2 (Affinity Capture-MS), ZMYM2 (Affinity Capture-MS), ZMYM2 (Affinity Capture-MS), ZMYM2 (Reconstituted Complex), PML (Affinity Capture-Western), ZMYM2 (Affinity Capture-Western), SUMO2 (Affinity Capture-Western), ZMYM2 (Co-fractionation)

ESM2 similar proteins: A0A1L8GR68, A2A791, B2GUN4, E1BP74, E1BZ85, F1QLG5, F7AQ22, O00472, O15164, O15550, O70546, O88974, O95789, P49140, P55265, P70365, Q14202, Q14596, Q15047, Q15788, Q4PJW2, Q5R413, Q5RC94, Q5RDJ2, Q5VZL5, Q64127, Q69Z66, Q6H8Q1, Q6KC51, Q6NXK2, Q6P3Y5, Q6PFK1, Q7Z3K3, Q8BJ34, Q8BL65, Q8BZH4, Q8CHY6, Q8IZD4, Q8TEW8, Q8VIG2

Diamond homologs: A2A791, A6QPH9, O95789, Q0P5J0, Q14202, Q2TAL8, Q3U2E2, Q3UA37, Q4R3D6, Q5RDJ2, Q5SVZ6, Q5VZL5, Q9CU65, Q9JLM4, Q9UBW7, Q9UJ78, A4Z943, A4Z944, A4Z945, P0CF97, Q49AG3, Q4R6P1, Q6R2W3, Q8IZ13, Q8TCP9

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
ZMYM2	“up-regulates activity”	MYBL2	binding
PLK1	down-regulates	ZMYM2	phosphorylation
ZMYM2	“down-regulates activity”	NANOG	binding
PLK1	“down-regulates quantity by destabilization”	ZMYM2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 179 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
Regulation of MECP2 expression and activity	5	15.7×	5e-03
Negative Regulation of CDH1 Gene Transcription	8	8.2×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — PRAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	45
Likely pathogenic	45
Uncertain significance	260
Likely benign	21
Benign	8

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1264312	NM_197968.4(ZMYM2):c.1618C>T (p.Arg540Ter)	Pathogenic
1309975	NM_197968.4(ZMYM2):c.1981C>T (p.Gln661Ter)	Pathogenic
1310444	NM_197968.4(ZMYM2):c.3119dup (p.Ser1041fs)	Pathogenic
1334524	NM_197968.4(ZMYM2):c.3532del (p.Ile1178fs)	Pathogenic
1373966	NM_197968.4(ZMYM2):c.1095del (p.His365fs)	Pathogenic
1455391	NM_197968.4(ZMYM2):c.1648C>T (p.Gln550Ter)	Pathogenic
1698733	NM_197968.4(ZMYM2):c.2833dup (p.Ala945fs)	Pathogenic
1703359	NM_197968.4(ZMYM2):c.3314dup (p.Leu1106fs)	Pathogenic
1708147	NM_197968.4(ZMYM2):c.1856dup (p.Ser620fs)	Pathogenic
1709371	NM_197968.4(ZMYM2):c.2700C>G (p.Tyr900Ter)	Pathogenic
1800812	NM_197968.4(ZMYM2):c.640_641dup (p.Thr215fs)	Pathogenic
1803263	NM_197968.4(ZMYM2):c.978del (p.Val327fs)	Pathogenic
2096321	NM_197968.4(ZMYM2):c.3336_3337del (p.Thr1114fs)	Pathogenic
2210008	NM_197968.4(ZMYM2):c.1129A>T (p.Lys377Ter)	Pathogenic
2226845	NM_197968.4(ZMYM2):c.1026_1027del (p.Gln342fs)	Pathogenic
2300685	NM_197968.4(ZMYM2):c.2727dup (p.Val910fs)	Pathogenic
2352145	NM_197968.4(ZMYM2):c.569T>G (p.Leu190Ter)	Pathogenic
2396225	NM_197968.4(ZMYM2):c.391C>T (p.Gln131Ter)	Pathogenic
2409857	NM_197968.4(ZMYM2):c.1615del (p.Cys539fs)	Pathogenic
2442527	NM_197968.4(ZMYM2):c.2054_2055del (p.Gln685fs)	Pathogenic
2570855	NM_197968.4(ZMYM2):c.1730C>G (p.Ser577Ter)	Pathogenic
2579151	NM_197968.4(ZMYM2):c.2494-2A>G	Pathogenic
2627843	NM_197968.4(ZMYM2):c.1013T>G (p.Leu338Ter)	Pathogenic
3048386	NM_197968.4(ZMYM2):c.421C>T (p.Arg141Ter)	Pathogenic
3075724	NM_197968.4(ZMYM2):c.1120_1121del (p.Val374fs)	Pathogenic
3251749	NM_197968.4(ZMYM2):c.3749del (p.Asn1250fs)	Pathogenic
3345893	NM_197968.4(ZMYM2):c.1977dup (p.His660fs)	Pathogenic
3382591	NM_197968.4(ZMYM2):c.1368T>G (p.Tyr456Ter)	Pathogenic
3767150	NM_197968.4(ZMYM2):c.339_342del (p.Ser114fs)	Pathogenic
3819561	NM_197968.4(ZMYM2):c.1008dup (p.Pro337fs)	Pathogenic

SpliceAI

5018 predictions. Top by Δscore:

Variant	Effect	Δscore
13:19960027:G:GG	donor_gain	1.0000
13:19993924:GCA:G	donor_gain	1.0000
13:19993927:G:GG	donor_gain	1.0000
13:20005070:TCA:T	acceptor_loss	1.0000
13:20005071:CAGA:C	acceptor_loss	1.0000
13:20005072:A:AG	acceptor_gain	1.0000
13:20005072:A:C	acceptor_loss	1.0000
13:20005073:G:GT	acceptor_gain	1.0000
13:20005073:GA:G	acceptor_gain	1.0000
13:20005073:GAGA:G	acceptor_gain	1.0000
13:20005073:GAGAT:G	acceptor_gain	1.0000
13:20005238:AG:A	donor_loss	1.0000
13:20005239:GG:G	donor_loss	1.0000
13:20005240:G:GA	donor_loss	1.0000
13:20005241:T:A	donor_loss	1.0000
13:20006368:TTTTA:T	acceptor_loss	1.0000
13:20006369:TTTAG:T	acceptor_loss	1.0000
13:20006371:TAGAT:T	acceptor_loss	1.0000
13:20006372:A:AG	acceptor_gain	1.0000
13:20006372:AG:A	acceptor_loss	1.0000
13:20006373:G:GA	acceptor_gain	1.0000
13:20006373:GATT:G	acceptor_gain	1.0000
13:20006373:GATTC:G	acceptor_gain	1.0000
13:20006585:AG:A	donor_loss	1.0000
13:20006586:GGT:G	donor_loss	1.0000
13:20006587:G:GA	donor_loss	1.0000
13:20006588:T:G	donor_loss	1.0000
13:20026604:A:G	acceptor_gain	1.0000
13:20026610:A:AG	acceptor_gain	1.0000
13:20026611:G:GG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000006956 (13:19904348 G>A), RS1000039908 (13:20041807 T>G), RS1000040654 (13:19923612 A>G,T), RS1000051809 (13:20077331 AT>A), RS1000054278 (13:19957642 G>A,C), RS1000076141 (13:19915588 C>T), RS1000076850 (13:19985983 C>T), RS1000121882 (13:20034709 T>C), RS1000135313 (13:19935935 G>A), RS1000141361 (13:19915383 C>A), RS1000143481 (13:19904613 C>G,T), RS1000149427 (13:19866541 T>G), RS1000164905 (13:19883977 A>C,G), RS1000187413 (13:20013408 C>CT), RS1000198218 (13:20053334 G>A)

Disease associations

OMIM: gene MIM:602221 | disease phenotypes: MIM:610805, MIM:619522, MIM:618835, MIM:610253

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities	Definitive	Autosomal dominant
congenital anomaly of kidney and urinary tract	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
syndromic complex neurodevelopmental disorder	Definitive	AD

Mondo (5): congenital anomaly of kidney and urinary tract (MONDO:0019719), neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities (MONDO:0859190), neurodevelopmental disorder (MONDO:0700092), combined oxidative phosphorylation deficiency 40 (MONDO:0030006), Kleefstra syndrome 1 (MONDO:0027407)

Orphanet (3): Renal or urinary tract malformation (Orphanet:93545), QRSL1-related combined oxidative phosphorylation defect (Orphanet:570491), Kleefstra syndrome (Orphanet:261494)

HPO phenotypes

73 total (30 of 73 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000028	Cryptorchidism
HP:0000034	Hydrocele testis
HP:0000041	Chordee
HP:0000047	Hypospadias
HP:0000074	Ureteropelvic junction obstruction
HP:0000104	Renal agenesis
HP:0000125	Pelvic kidney
HP:0000126	Hydronephrosis
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000325	Triangular face
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000385	Small earlobe
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000475	Broad neck
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000540	Hypermetropia
HP:0000670	Carious teeth
HP:0000709	Psychosis
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004729_1	Facial emotion recognition (happy faces)	3.000000e-06
GCST005830_57	Hand grip strength	1.000000e-08
GCST010988_460	Adult body size	2.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008329	facial emotion recognition measurement
EFO:0006941	grip strength measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C566906	Cakut (supp.)
C563043	Kleefstra Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, decreases methylation, affects cotreatment	9
bisphenol A	decreases expression, decreases methylation, affects cotreatment	3
sodium arsenite	decreases expression, increases expression	2
epigallocatechin gallate	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
urushiol	increases expression	1
methylmercuric chloride	decreases expression	1
sodium arsenate	decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	decreases reaction, affects binding	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	decreases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases expression, affects cotreatment	1
jinfukang	decreases expression	1
LDN 193189	decreases expression, affects cotreatment	1
NSC 689534	affects binding, increases expression	1
Resveratrol	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT04115345	PHASE1	COMPLETED	A Study of a Renal Autologous Cell Therapy (REACT) in Patients With Chronic Kidney Disease (CKD) From Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).
NCT05694169	PHASE1	TERMINATED	A Study of Participants With Chronic Kidney Disease Previously Treated With REACT
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT04537364	Not specified	COMPLETED	Prediction of Renal Parenchymal Damage of CAKUT
NCT06921733	Not specified	RECRUITING	Ultrasound Localization Microscopy in Patient With Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase