SHLD2

Summary

SHLD2 (shieldin complex subunit 2, HGNC:28773) is a protein-coding gene on chromosome 10q23.2, encoding Shieldin complex subunit 2 (Q86V20). Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs). It is a selective cancer dependency (DepMap: 11.7% of cell lines).

Involved in negative regulation of double-strand break repair via homologous recombination; positive regulation of double-strand break repair via nonhomologous end joining; and positive regulation of isotype switching. Located in actin cytoskeleton; nucleoplasm; and site of double-strand break.

Source: NCBI Gene 54537 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 136 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 11.7% of screened cell lines
• MANE Select transcript: NM_001330112

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28773
Approved symbol	SHLD2
Name	shieldin complex subunit 2
Location	10q23.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC5560, bA163M19.1, FAM35A1, RINN2
Ensembl gene	ENSG00000122376
Ensembl biotype	protein_coding
OMIM	618029
Entrez	54537

Gene structure

Transcript identifiers

Ensembl transcripts: 123 — 123 protein_coding

ENST00000298784, ENST00000298786, ENST00000437629, ENST00000898040, ENST00000898041, ENST00000898042, ENST00000898043, ENST00000898044, ENST00000898045, ENST00000898046, ENST00000898047, ENST00000898048, ENST00000898049, ENST00000898050, ENST00000898051, ENST00000898052, ENST00000898053, ENST00000898054, ENST00000898055, ENST00000898056, ENST00000898057, ENST00000898058, ENST00000898059, ENST00000898060, ENST00000898061, ENST00000898062, ENST00000898063, ENST00000898064, ENST00000898065, ENST00000898066, ENST00000898067, ENST00000898068, ENST00000898069, ENST00000898070, ENST00000898071, ENST00000898072, ENST00000898073, ENST00000898074, ENST00000898075, ENST00000898076, ENST00000898077, ENST00000898078, ENST00000898079, ENST00000898080, ENST00000898081, ENST00000898082, ENST00000898083, ENST00000898084, ENST00000898085, ENST00000898086, ENST00000898087, ENST00000898088, ENST00000898089, ENST00000898090, ENST00000898091, ENST00000898092, ENST00000898093, ENST00000898094, ENST00000898095, ENST00000898096, ENST00000898097, ENST00000898098, ENST00000898099, ENST00000898100, ENST00000898101, ENST00000898102, ENST00000898103, ENST00000898104, ENST00000898105, ENST00000898106, ENST00000898107, ENST00000898108, ENST00000898109, ENST00000898110, ENST00000898111, ENST00000898112, ENST00000914814, ENST00000914815, ENST00000914816, ENST00000914817, ENST00000914818, ENST00000914819, ENST00000914820, ENST00000914821, ENST00000914822, ENST00000914823, ENST00000914824, ENST00000914825, ENST00000914826, ENST00000943970, ENST00000943971, ENST00000943972, ENST00000943973, ENST00000943974, ENST00000943975, ENST00000943976, ENST00000943977, ENST00000943978, ENST00000943979, ENST00000943980, ENST00000943981, ENST00000943982, ENST00000943983, ENST00000943984, ENST00000943985, ENST00000943986, ENST00000943987, ENST00000943988, ENST00000943989, ENST00000943990, ENST00000943991, ENST00000943992, ENST00000943993, ENST00000943994, ENST00000943995, ENST00000943996, ENST00000943997, ENST00000943998, ENST00000943999, ENST00000944000, ENST00000944001, ENST00000944002, ENST00000944003

RefSeq mRNA: 17 — MANE Select: NM_001330112 NM_001330112, NM_001377158, NM_001377159, NM_001377160, NM_001377161, NM_001377162, NM_001377163, NM_001377164, NM_001377165, NM_001377166, NM_001377167, NM_001377168, NM_001377169, NM_001377170, NM_001377171, NM_001377172, NM_019054

CCDS: CCDS7383, CCDS81484

Canonical transcript exons

ENST00000298786 — 10 exons

Exon	Start	End
ENSE00001142809	87151350	87152879
ENSE00001210044	87170478	87170672
ENSE00001244957	87190484	87191465
ENSE00002460087	87175889	87176095
ENSE00002468332	87170840	87170974
ENSE00002475812	87187085	87187200
ENSE00002513474	87158048	87158155
ENSE00002529023	87180075	87180303
ENSE00003695709	87096934	87096989
ENSE00003908951	87095206	87095248

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 92.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.1164 / max 155.1186, expressed in 1740 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106016	9.6855	1730
106015	0.4310	219

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	92.61	gold quality
endometrium	UBERON:0001295	89.24	gold quality
duodenum	UBERON:0002114	89.23	gold quality
liver	UBERON:0002107	88.13	gold quality
islet of Langerhans	UBERON:0000006	87.93	gold quality
adult mammalian kidney	UBERON:0000082	87.83	gold quality
right adrenal gland cortex	UBERON:0035827	87.66	gold quality
left adrenal gland cortex	UBERON:0035825	87.44	gold quality
left adrenal gland	UBERON:0001234	87.34	gold quality
right lobe of liver	UBERON:0001114	87.31	gold quality
right adrenal gland	UBERON:0001233	87.31	gold quality
adrenal gland	UBERON:0002369	87.29	gold quality
rectum	UBERON:0001052	87.13	gold quality
kidney	UBERON:0002113	86.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.29	gold quality
adrenal tissue	UBERON:0018303	86.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.87	gold quality
cortex of kidney	UBERON:0001225	85.72	gold quality
thyroid gland	UBERON:0002046	85.46	gold quality
right lobe of thyroid gland	UBERON:0001119	85.37	gold quality
left lobe of thyroid gland	UBERON:0001120	85.25	gold quality
metanephros cortex	UBERON:0010533	85.11	gold quality
smooth muscle tissue	UBERON:0001135	85.09	gold quality
leukocyte	CL:0000738	84.98	gold quality
pancreas	UBERON:0001264	84.92	gold quality
monocyte	CL:0000576	84.88	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.78	gold quality
cortical plate	UBERON:0005343	84.63	gold quality
uterus	UBERON:0000995	84.26	gold quality
mammary gland	UBERON:0001911	84.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	yes	14.05
E-ANND-3	yes	4.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting SHLD2, 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-4668-3P	100.00	68.74	2635
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-6080	99.43	69.43	373
HSA-MIR-942-5P	99.41	68.40	1977

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• the FAM35A locus showed an association with all gout by meta-analysis among the Japanese, Caucasian and NZ Polynesian sample sets at a genome-wide level of significance. (PMID:27899376)
• found FAM35A, a previously unstudied protein with an unstructured N-terminal region and a C-terminal region harboring three OB-fold domains similar to single-stranded DNA-binding protein RPA, as novel interactor of REV7/RIF1/53BP1. (PMID:29789392)
• Genetic association and functional analysis of rs7903456 in FAM35A gene and hyperuricemia (PMID:29942023)
• these results establish SHLD2 as a novel effector of REV7 in controlling the decision-making process during DSB repair. (PMID:30154076)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	shld2	ENSDARG00000038686
mus_musculus	Shld2	ENSMUSG00000041471
rattus_norvegicus	Shld2	ENSRNOG00000059057

Protein

Protein identifiers

Shieldin complex subunit 2 — Q86V20 (reviewed: Q86V20)

Alternative names: Protein FAM35A, RINN1-REV7-interacting novel NHEJ regulator 2, Shield complex subunit 2

All UniProt accessions (2): Q86V20, U3KQ89

UniProt curated annotations — full annotation on UniProt →

Function. Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs). During G1 and S phase of the cell cycle, the complex functions downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection. Mediates various NHEJ-dependent processes including immunoglobulin class-switch recombination, and fusion of unprotected telomeres.

Subunit / interactions. Component of the shieldin complex, consisting of SHLD1, SHLD2, SHLD3 and MAD2L2/REV7. Within the complex, SHLD2 forms a scaffold which interacts with a SHLD3-MAD2L2 subcomplex via its N-terminus, and with SHLD1 via its C-terminus. Interacts with TP53BP1. Interacts with RIF1. Interacts with ASTE1.

Subcellular location. Nucleus. Chromosome.

Miscellaneous. In BRCA1-deficient cells, function of the shieldin complex is necessary for sensitivity to camptothecin and the PARP inhibitor olaparib.

Similarity. Belongs to the SHLD2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86V20-1	1	yes
Q86V20-2	2

RefSeq proteins (17): NP_001317041, NP_001364087, NP_001364088, NP_001364089, NP_001364090, NP_001364091, NP_001364092, NP_001364093, NP_001364094, NP_001364095, NP_001364096, NP_001364097, NP_001364098, NP_001364099, NP_001364100, NP_001364101, NP_061927 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029715	FAM35A	Family
IPR031589	SHLD2_C	Domain
IPR049507	SHLD2_OB1	Domain
IPR053944	SHLD2_OB2	Domain

Pfam: PF15793, PF21669, PF22779

UniProt features (13 total): region of interest 3, sequence variant 3, sequence conflict 2, strand 2, chain 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6KTO	X-RAY DIFFRACTION	3.45
7L9P	ELECTRON MICROSCOPY	3.6
6WWA	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86V20-F1	55.77	0.15

Functional residue map

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

Mutagenesis-validated functional residues (1):

Position	Phenotype
6–11	fails to interact with shld3 or mad2l2.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 146 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_B_CELL_ACTIVATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_DNA_REPAIR, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION, GOBP_TELOMERE_ORGANIZATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_POSITIVE_REGULATION_OF_B_CELL_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_B_CELL_MEDIATED_IMMUNITY

GO Biological Process (8): somatic diversification of immunoglobulins involved in immune response (GO:0002208), DNA repair (GO:0006281), regulation of double-strand break repair via homologous recombination (GO:0010569), telomere maintenance in response to DNA damage (GO:0043247), positive regulation of isotype switching (GO:0045830), negative regulation of double-strand break repair via homologous recombination (GO:2000042), positive regulation of double-strand break repair via nonhomologous end joining (GO:2001034), DNA damage response (GO:0006974)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), actin cytoskeleton (GO:0015629), site of double-strand break (GO:0035861)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA damage response	2
double-strand break repair via homologous recombination	2
cellular anatomical structure	2
immunoglobulin production involved in immunoglobulin-mediated immune response	1
somatic diversification of immunoglobulins	1
DNA metabolic process	1
regulation of DNA recombination	1
regulation of double-strand break repair	1
telomere maintenance	1
positive regulation of immunoglobulin production	1
positive regulation of immunoglobulin mediated immune response	1
isotype switching	1
regulation of isotype switching	1
positive regulation of DNA recombination	1
positive regulation of B cell activation	1
positive regulation of developmental process	1
regulation of double-strand break repair via homologous recombination	1
negative regulation of DNA recombination	1
negative regulation of double-strand break repair	1
double-strand break repair via nonhomologous end joining	1
positive regulation of double-strand break repair	1
regulation of double-strand break repair via nonhomologous end joining	1
cellular response to stress	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoskeleton	1
site of DNA damage	1

Protein interactions and networks

STRING

438 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SHLD2	SHLD1	Q8IYI0	998
SHLD2	MAD2L2	Q9UI95	996
SHLD2	SHLD3	Q6ZNX1	995
SHLD2	TP53BP1	Q12888	762
SHLD2	REV3L	O60673	716
SHLD2	C20orf96	Q9NUD7	692
SHLD2	CTC1	Q2NKJ3	662
SHLD2	PAXIP1	Q6ZW49	581
SHLD2	POLQ	O75417	573
SHLD2	PAXX	Q9BUH6	572
SHLD2	RBBP8	Q99708	568
SHLD2	BRCA1	P38398	528
SHLD2	EXO1	Q9UQ84	513
SHLD2	NIPAL1	Q6NVV3	511
SHLD2	TRIP13	Q15645	505

IntAct

10 interactions, top by confidence:

A	B	Type	Score
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
SHLD2	SHLD1	psi-mi:“MI:0915”(physical association)	0.500
SHLD2	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
Mad2l2	CALU	psi-mi:“MI:0915”(physical association)	0.400
Mad2l2	CHD1	psi-mi:“MI:0914”(association)	0.350
SHLD2	SHLD3	psi-mi:“MI:0914”(association)	0.350
SHLD3	SHLD2	psi-mi:“MI:0914”(association)	0.350
alaS	SHLD2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (69): FAM35A (Affinity Capture-MS), FAM35A (Affinity Capture-MS), FAM35A (Affinity Capture-MS), FAM35A (Affinity Capture-RNA), MAD2L2 (Affinity Capture-Western), C20orf196 (Affinity Capture-Western), C20orf196 (Co-localization), MAD2L2 (Co-localization), FAM35A (Co-localization), FAM35A (Co-localization), FAM35A (Affinity Capture-MS), FAM35A (Affinity Capture-MS), EIF3CL (Affinity Capture-MS), MAD2L2 (Affinity Capture-MS), FAM50A (Affinity Capture-MS)

ESM2 similar proteins: A0A0M3U1B0, A0A1L8EYB2, A0JMF7, A2AGB2, A2AKX3, A2ALV5, A6QNQ6, A8MT70, B0S6S9, B1WC58, D3Z987, F6SNN2, P56716, P70347, Q0P5X5, Q28FY7, Q2M2Z5, Q3U0P1, Q3V089, Q5CZC0, Q5DTT3, Q5RCM2, Q5T1N1, Q5T4T6, Q5VWN6, Q5VXU9, Q5W0Q7, Q69ZR9, Q6ZP01, Q7Z333, Q7Z4H7, Q7ZZH7, Q80WQ8, Q86V20, Q86YC2, Q8CCC3, Q8R3P9, Q8WP21, Q92844, Q96QP1

Diamond homologs: Q3UEN2, Q5RCM2, Q86V20

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	107
Likely benign	15
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2422865	NC_000010.10:g.(?88428449)(89725229_?)del	Pathogenic

SpliceAI

2056 predictions. Top by Δscore:

Variant	Effect	Δscore
10:87094323:ACCTC:A	donor_gain	1.0000
10:87094324:CCTCC:C	donor_gain	1.0000
10:87094327:C:A	donor_gain	1.0000
10:87095248:GGTA:G	donor_loss	1.0000
10:87096932:A:AG	acceptor_gain	1.0000
10:87096933:G:GG	acceptor_gain	1.0000
10:87158152:GAAT:G	donor_gain	1.0000
10:87158156:G:GG	donor_gain	1.0000
10:87170837:CA:C	acceptor_loss	1.0000
10:87170838:A:AG	acceptor_gain	1.0000
10:87170838:AGAG:A	acceptor_gain	1.0000
10:87170839:G:GG	acceptor_gain	1.0000
10:87170839:GA:G	acceptor_gain	1.0000
10:87170839:GAGG:G	acceptor_gain	1.0000
10:87170839:GAGGC:G	acceptor_gain	1.0000
10:87170975:GTA:G	donor_loss	1.0000
10:87170976:T:G	donor_loss	1.0000
10:87187197:A:G	donor_gain	1.0000
10:87187197:ATAG:A	donor_gain	1.0000
10:87187197:ATAGG:A	donor_loss	1.0000
10:87187199:AGGT:A	donor_loss	1.0000
10:87187200:GGT:G	donor_loss	1.0000
10:87187202:T:G	donor_loss	1.0000
10:87094319:GCTCA:G	donor_loss	0.9900
10:87094320:CTCA:C	donor_loss	0.9900
10:87094321:TCA:T	donor_loss	0.9900
10:87094322:CA:C	donor_loss	0.9900
10:87094323:ACCT:A	donor_gain	0.9900
10:87094324:C:A	donor_loss	0.9900
10:87094324:CCTC:C	donor_gain	0.9900

AlphaMissense

6000 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:87158107:A:C	S529R	0.986
10:87158109:T:A	S529R	0.986
10:87158109:T:G	S529R	0.986
10:87170929:T:A	W640R	0.980
10:87170929:T:C	W640R	0.980
10:87152099:A:C	S249R	0.974
10:87152101:C:A	S249R	0.974
10:87152101:C:G	S249R	0.974
10:87152078:T:C	F242L	0.965
10:87152080:T:A	F242L	0.965
10:87152080:T:G	F242L	0.965
10:87151382:T:C	F10L	0.964
10:87151384:T:A	F10L	0.964
10:87151384:T:G	F10L	0.964
10:87152768:G:C	A472P	0.963
10:87170891:T:A	V627E	0.963
10:87170927:T:C	L639S	0.963
10:87170885:T:C	L625S	0.962
10:87170931:G:C	W640C	0.961
10:87170931:G:T	W640C	0.961
10:87152862:A:T	D503V	0.957
10:87152832:C:A	A493E	0.956
10:87180260:T:C	C717R	0.956
10:87190526:T:C	L784P	0.955
10:87158114:T:C	L531S	0.953
10:87152861:G:C	D503H	0.951
10:87170932:G:C	G641R	0.951
10:87152684:T:C	C444R	0.950
10:87152862:A:C	D503A	0.949
10:87180206:T:C	C699R	0.949

dbSNP variants (sampled 300 via entrez): RS1000035261 (10:87157077 C>T), RS1000048497 (10:87105610 T>A), RS1000099094 (10:87150021 A>T), RS1000103772 (10:87107766 G>T), RS1000147957 (10:87157477 C>A,G), RS1000169748 (10:87148744 AAAAAT>A), RS1000227859 (10:87143869 T>C), RS1000227882 (10:87156033 A>G,T), RS1000315964 (10:87093370 A>G), RS1000377540 (10:87164620 A>C), RS1000447006 (10:87184210 A>G), RS1000519944 (10:87112491 A>C), RS1000546478 (10:87152291 T>C), RS1000560339 (10:87145488 CTTCT>C), RS1000596195 (10:87107399 A>C)

Disease associations

OMIM: gene MIM:618029 | disease phenotypes: MIM:606762

GenCC curated gene-disease

Mondo (2): hyperinsulinism-hyperammonemia syndrome (MONDO:0011717), PTEN hamartoma tumor syndrome (MONDO:0017623)

Orphanet (2): Hyperinsulinism-hyperammonemia syndrome (Orphanet:35878), PTEN hamartoma tumor syndrome (Orphanet:306498)

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST003925_1	Gout	4.000000e-08
GCST003925_8	Gout	6.000000e-07
GCST003926_6	Renal underexcretion gout	4.000000e-08
GCST005983_35	Serum uric acid levels	4.000000e-11
GCST007725_6	Serum uric acid levels	4.000000e-12
GCST008058_307	Estimated glomerular filtration rate	1.000000e-08
GCST008971_2	Urate levels	1.000000e-11
GCST008972_52	Urate levels	1.000000e-10
GCST008972_79	Urate levels	1.000000e-20
GCST010083_50	Hemoglobin levels	3.000000e-10
GCST010274_2	Gout (combined type)	4.000000e-11
GCST010276_13	Renal underexcretion gout	9.000000e-11
GCST010277_3	Gout	4.000000e-17
GCST90002383_491	Hematocrit	9.000000e-12
GCST90002384_270	Hemoglobin	6.000000e-12
GCST90002403_268	Red blood cell count	2.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004761	uric acid measurement
EFO:0004531	urate measurement
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538375	Hyperinsulinemic hypoglycemia, familial, 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Valproic Acid	decreases expression, increases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Thiram	decreases expression	1
Ursodeoxycholic Acid	affects expression	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
Aflatoxin B1	decreases methylation	1
Aflatoxin M1	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04984798	PHASE2	WITHDRAWN	Vitamin E Efficacy in HI/HA
NCT04094675	PHASE2	COMPLETED	Sirolimus for Cowden Syndrome With Colon Polyposis
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT03797222	Not specified	COMPLETED	Vitamin E Supplementation in Hyperinsulinism/Hyperammonemia Syndrome
NCT07218575	PHASE2/PHASE3	NOT_YET_RECRUITING	Double-Blind Trial of Everolimus for Improving Social Abilities in PTEN Germline Mutations
NCT02991807	PHASE1/PHASE2	COMPLETED	RAD001 and Neurocognition in PTEN Hamartoma Tumor Syndrome
NCT06080165	PHASE1/PHASE2	WITHDRAWN	Sirolimus for Improving Social Abilities in People With PTEN Germline Mutations
NCT02461446	Not specified	RECRUITING	Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03630523	Not specified	UNKNOWN	Response of Immune System to Flu Vaccination in PHTS
NCT05671107	Not specified	COMPLETED	Development and Validation of an Online Neurobehavioral Evaluation Tool for PTEN Patients
NCT06462430	Not specified	RECRUITING	PTEN Hamartoma Tumor Syndrome Pediatric Patient Registry