PRDM5

Summary

PRDM5 (PR/SET domain 5, HGNC:9349) is a protein-coding gene on chromosome 4q27, encoding PR domain zinc finger protein 5 (Q9NQX1). Sequence-specific DNA-binding transcription factor.

The protein encoded by this gene is a transcription factor of the PR-domain protein family. It contains a PR-domain and multiple zinc finger motifs. Transcription factors of the PR-domain family are known to be involved in cell differentiation and tumorigenesis.

Source: NCBI Gene 11107 — RefSeq curated summary.

At a glance

• Gene–disease (curated): brittle cornea syndrome 2 (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 860 total — 32 pathogenic, 27 likely-pathogenic
• Phenotypes (HPO): 45
• MANE Select transcript: NM_018699

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9349
Approved symbol	PRDM5
Name	PR/SET domain 5
Location	4q27
Locus type	gene with protein product
Status	Approved
Aliases	PFM2
Ensembl gene	ENSG00000138738
Ensembl biotype	protein_coding
OMIM	614161
Entrez	11107

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000264808, ENST00000394435, ENST00000428209, ENST00000502409, ENST00000503661, ENST00000505033, ENST00000505484, ENST00000506065, ENST00000507611, ENST00000512845, ENST00000513741, ENST00000515109, ENST00000898038, ENST00000898039, ENST00000940461, ENST00000940462, ENST00000940463

RefSeq mRNA: 5 — MANE Select: NM_018699 NM_001300823, NM_001300824, NM_001379104, NM_001379106, NM_018699

CCDS: CCDS3716, CCDS75187, CCDS75188

Canonical transcript exons

ENST00000264808 — 16 exons

Exon	Start	End
ENSE00001081499	120816832	120816924
ENSE00001081506	120816453	120816574
ENSE00001855177	120691915	120695275
ENSE00002073405	120922516	120922726
ENSE00003461944	120799661	120799745
ENSE00003465599	120710309	120710413
ENSE00003484471	120781143	120781303
ENSE00003505053	120777188	120777281
ENSE00003508489	120811370	120811449
ENSE00003530712	120784998	120785091
ENSE00003552770	120907474	120907557
ENSE00003590315	120818353	120818527
ENSE00003600823	120853418	120853540
ENSE00003604782	120798267	120798424
ENSE00003660927	120821171	120821345
ENSE00003693697	120754553	120754638

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 93.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.9009 / max 48.4918, expressed in 1122 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53785	1.7041	863
53786	1.1968	777

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	93.84	gold quality
sural nerve	UBERON:0015488	89.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.82	gold quality
left ovary	UBERON:0002119	84.50	gold quality
right ovary	UBERON:0002118	83.53	gold quality
adrenal tissue	UBERON:0018303	83.50	gold quality
body of pancreas	UBERON:0001150	82.19	gold quality
body of uterus	UBERON:0009853	80.64	gold quality
ovary	UBERON:0000992	80.57	gold quality
tibia	UBERON:0000979	80.49	gold quality
endocervix	UBERON:0000458	80.00	gold quality
descending thoracic aorta	UBERON:0002345	79.51	gold quality
nerve	UBERON:0001021	79.42	gold quality
tibial nerve	UBERON:0001323	79.42	gold quality
stromal cell of endometrium	CL:0002255	79.39	gold quality
ectocervix	UBERON:0012249	79.01	gold quality
ascending aorta	UBERON:0001496	78.73	gold quality
popliteal artery	UBERON:0002250	78.73	gold quality
tibial artery	UBERON:0007610	78.72	gold quality
thoracic aorta	UBERON:0001515	78.68	gold quality
right uterine tube	UBERON:0001302	78.54	gold quality
aorta	UBERON:0000947	78.49	gold quality
pancreas	UBERON:0001264	78.39	gold quality
colonic epithelium	UBERON:0000397	78.30	gold quality
left uterine tube	UBERON:0001303	78.25	gold quality
left lobe of thyroid gland	UBERON:0001120	78.20	gold quality
mucosa of stomach	UBERON:0001199	77.58	gold quality
adenohypophysis	UBERON:0002196	77.54	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	77.47	gold quality
left adrenal gland cortex	UBERON:0035825	77.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.78

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
APC
GFI1
MGLL
PRDM5

Upstream regulators (CollecTRI, top): FOXN1, GFI1, HNF4A, PRDM5

miRNA regulators (miRDB)

131 targeting PRDM5, 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-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-450B-5P	99.92	71.48	3175

Literature-anchored findings (GeneRIF, showing 23)

• PRDM5 caused G2/M arrest and apoptosis upon infection of tumor cells. These results suggest that inactivation of PRDM5 may play a role in carcinogenesis. (PMID:15077163)
• Results identify PRDM5, which acts as a sequence-specific, DNA binding transcription factor that targets hematopoiesis-associated protein-coding and microRNA genes, some of which are targets of Gfi1. (PMID:17636019)
• Data suggest that epigenetic alteration of PRDM5 (e.g., methylation of its 5’-CpG island or trimethylation of Lys(27) of histone H3) likely plays a key role in the progression of gastrointestinal cancers and may be a useful molecular marker. (PMID:17699856)
• Data show that reduced expression of PRDM5 may play an important role in the pathogenesis and/or development of cervical cancer, and is considered to be caused in part by aberrant DNA methylation. (PMID:20213097)
• ZNF469 and PRDM5, two genes that when mutated cause brittle cornea syndrome, participate in the same regulatory pathway. (PMID:21664999)
• Frequent epigenetic silencing of PRDM5 is involved in multiple tumorigeneses, which could serve as a tumor biomarker (PMID:22087297)
• Data provide the first causal link between Prdm5 loss and intestinal carcinogenesis, and uncover an extensive and novel PRDM5 target repertoire likely facilitating the tumor-suppressive functions of PRDM5. (PMID:23873026)
• Promoter methylation-mediated downregulation of PRDM5 contributes to the development of lung squamous cell carcinoma. (PMID:24395656)
• PRDM2, PRDM5, PRDM16 promoters are methylated and their expression is suppressed in lung cancer cells. (PMID:24966940)
• These data suggest that PRDM5 is a relevant tumour suppressor gene that is frequently targeted in colorectal tumourigenesis. (PMID:25613750)
• Defective interaction of PRDM5 with repressive complexes, and dysregulation of H3K9me2, play a role in PRDM5-associated disease. (PMID:26395458)
• Genetic variants in PRDM5 can lead to various syndromic and nonsyndromic disorders affecting the anterior segment of the eye. (PMID:26489929)
• Reduced expression of PRDM5 was observed in the cornea and retina of brittle cornea syndrome patients. (PMID:26560304)
• The current study revealed a novel mutation in the PRDM5 gene in a Brittle cornea syndrome (BCS) family and recurrent mutation in a sporadic BCS patient. (PMID:27032025)
• The miR-182 promoter is rarely methylated in epithelial ovarian cancers (EOCs), and its methylation status is associated with lower miR-182 expression. Deletion of the PRDM5 locus may play a supportive role in miR-182 overexpression in EOC. miR-182 is an unfavorable prognostic factor in EOC. (PMID:27295517)
• Both Prdm 4 and Prdm 5 are expressed in human corneal endothelium, primary hCECs and in HCECs-12 cells, characterised by expression of the Na(+)/K(+)-ATPase. (PMID:28228349)
• Inhibiting PRDM5 expression by siRNA attenuated the IFN-gamma-triggered accumulation of active caspase-3 and cleaved PARP in intestinal epithelial cells. Moreover, flow cytometry assay and CCK-8 analysis revealed that PRDM5 knockdown significantly alleviated the IFN-gamma-induced cellular apoptosis in HT29 cells. (PMID:28476379)
• Truncations may be the primary mutation type in PITX2. Glaucoma onset may be earlier in patients with mutations in PITX2 than in those without mutations in PITX2 and FOXC1. A block of the anterior chamber angle by the end of the iris might represent the main factor influencing the development of glaucoma in ARS patients with an asymmetric aniridia phenotype. (PMID:29939776)
• Silencing of PRDM5 increases cell proliferation and inhibits cell apoptosis in glioma. (PMID:32083978)
• More than meets the eye: Expanding and reviewing the clinical and mutational spectrum of brittle cornea syndrome. (PMID:33739556)
• PRDM5 suppresses oesophageal squamous carcinoma cells and modulates 14-3-3zeta/Akt signalling pathway. (PMID:34757658)
• Low expression of PRDM5 predicts poor prognosis of esophageal squamous cell carcinoma. (PMID:35799142)
• Deregulation of PRDM5 promotes cell proliferation by regulating JAK/STAT signaling pathway through SOCS1 in human lung adenocarcinoma. (PMID:36127737)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	prdm5	ENSDARG00000006288
mus_musculus	Prdm5	ENSMUSG00000029913
rattus_norvegicus	Prdm5	ENSRNOG00000023679

Paralogs (4): ZNF668 (ENSG00000167394), ZNF358 (ENSG00000198816), ZNF579 (ENSG00000218891), ZNF850 (ENSG00000267041)

Protein

Protein identifiers

PR domain zinc finger protein 5 — Q9NQX1 (reviewed: Q9NQX1)

Alternative names: PR domain-containing protein 5

All UniProt accessions (2): Q9NQX1, H0Y9S1

UniProt curated annotations — full annotation on UniProt →

Function. Sequence-specific DNA-binding transcription factor. Represses transcription at least in part by recruitment of the histone methyltransferase EHMT2/G9A and histone deacetylases such as HDAC1. Regulates hematopoiesis-associated protein-coding and microRNA (miRNA) genes. May regulate the expression of proteins involved in extracellular matrix development and maintenance, including fibrillar collagens, such as COL4A1 and COL11A1, connective tissue components, such as HAPLN1, and molecules regulating cell migration and adhesion, including EDIL3 and TGFB2. May cause G2/M arrest and apoptosis in cancer cells.

Subunit / interactions. Interacts with EHMT2/G9A, GFI1 and HDAC1.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed with highest levels in colon and ovary. Tends to be silenced in breast, colorectal, gastric and liver cancer tissues.

Disease relevance. Brittle cornea syndrome 2 (BCS2) [MIM:614170] A disorder characterized by extreme corneal thinning resulting in corneal rupture after minor trauma, blue sclerae, keratoconus or keratoglobus, hyperelasticity of the skin, and hypermobile joints. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the class V-like SAM-binding methyltransferase superfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NQX1-1	1	yes
Q9NQX1-2	2
Q9NQX1-3	3
Q9NQX1-4	4

RefSeq proteins (5): NP_001287752, NP_001287753, NP_001366033, NP_001366035, NP_061169* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR013087	Znf_C2H2_type	Domain
IPR017125	Znf_PRDM5-like	Family
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR044415	PRDM5_PR-SET	Domain
IPR046341	SET_dom_sf	Homologous_superfamily
IPR050331	Zinc_finger_PRDM4/PRDM1/PRDM14	Family

Pfam: PF00096, PF12874, PF13912, PF21549

UniProt features (37 total): zinc finger region 16, strand 9, splice variant 5, helix 2, chain 1, domain 1, sequence variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6XAZ	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQX1-F1	72.53	0.12

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 220 (showing top): GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_EXTRACELLULAR_MATRIX_ORGANIZATION, GOBP_MITOTIC_CELL_CYCLE, LEE_AGING_CEREBELLUM_DN, RGAGGAARY_PU1_Q6, GOBP_METHYLATION, GOCC_NUCLEAR_BODY, GOCC_NUCLEOLUS, ZHAN_MULTIPLE_MYELOMA_CD2_UP, ZHAN_MULTIPLE_MYELOMA_MS_DN, MZF1_01, GOMF_TRANSCRIPTION_FACTOR_BINDING, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_ONE_CARBON_GROUPS, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, WONG_ADULT_TISSUE_STEM_MODULE

GO Biological Process (9): negative regulation of transcription by RNA polymerase II (GO:0000122), mitotic cell cycle (GO:0000278), chromatin organization (GO:0006325), methylation (GO:0032259), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of extracellular matrix organization (GO:1903053), cellular response to leukemia inhibitory factor (GO:1990830), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (13): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), methyltransferase activity (GO:0008168), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), DNA-binding transcription factor binding (GO:0140297), DNA binding (GO:0003677), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), nuclear body (GO:0016604)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
nuclear lumen	2
intracellular membraneless organelle	2
negative regulation of DNA-templated transcription	1
cell cycle	1
mitotic nuclear division	1
cellular component organization	1
metabolic process	1
negative regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
extracellular matrix organization	1
regulation of cellular component organization	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transcription regulator activity	1
transferase activity, transferring one-carbon groups	1
transition metal ion binding	1
DNA binding	1
transcription factor binding	1
nucleic acid binding	1
binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
nucleoplasm	1

Protein interactions and networks

STRING

1208 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRDM5	GTF3C1	Q12789	625
PRDM5	PRDM8	Q9NQV8	622
PRDM5	FKBP14	Q9NWM8	558
PRDM5	PRDM11	Q9NQV5	538
PRDM5	B4GALT7	Q9UBV7	533
PRDM5	MLF1	P58340	519
PRDM5	ADAM23	O75077	515
PRDM5	CHST14	Q8NCH0	515
PRDM5	SLC39A13	Q96H72	506
PRDM5	HNMT	P50135	480
PRDM5	B3GALT6	Q96L58	475
PRDM5	COL11A1	P12107	468
PRDM5	EHMT2	Q96KQ7	464
PRDM5	PLOD1	Q02809	459
PRDM5	PRDM7	Q9NQW5	447

IntAct

13 interactions, top by confidence:

A	B	Type	Score
PRDM5	HDAC1	psi-mi:“MI:0915”(physical association)	0.580
PRDM5	HDAC1	psi-mi:“MI:0914”(association)	0.580
GFI1	PRDM5	psi-mi:“MI:0915”(physical association)	0.510
PRDM5	GFI1	psi-mi:“MI:0915”(physical association)	0.510
PRDM5	EHMT2	psi-mi:“MI:0915”(physical association)	0.500
PRDM5	TFAP4	psi-mi:“MI:0915”(physical association)	0.370
PRDM5	PRSS1	psi-mi:“MI:0914”(association)	0.350
ABT1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
PRDM5	CASC3	psi-mi:“MI:0914”(association)	0.350
PRDM5	CMAS	psi-mi:“MI:0914”(association)	0.350

BioGRID (82): CCDC77 (Affinity Capture-MS), FAM102B (Affinity Capture-MS), FBXO11 (Affinity Capture-MS), ZNF687 (Affinity Capture-MS), THAP11 (Affinity Capture-MS), TNRC18 (Affinity Capture-MS), YBX2 (Affinity Capture-MS), ABT1 (Affinity Capture-MS), ZFP91 (Affinity Capture-MS), ZBTB4 (Affinity Capture-MS), BAG1 (Affinity Capture-MS), RPL26L1 (Affinity Capture-MS), WHSC1 (Affinity Capture-MS), RBM34 (Affinity Capture-MS), RPL10A (Affinity Capture-MS)

ESM2 similar proteins: A8WLV5, E0X9N4, O42395, O65639, P09052, P24346, P34689, P36627, P53849, P53996, P62633, P62634, P91599, P92186, Q04832, Q09476, Q0JD07, Q18034, Q3MSQ8, Q3T0Q6, Q4JG17, Q4R5S7, Q54NW4, Q5NU13, Q5R5R5, Q5W5U4, Q5ZA07, Q61496, Q64060, Q67YE6, Q6GWX0, Q6IDS6, Q7F8R0, Q7XPK1, Q84MZ4, Q8T8R1, Q8VZ42, Q8WW36, Q91372, Q94C69

Diamond homologs: A0A163UT06, A2AJ77, A6QPM3, E9Q3T6, O75626, P14404, Q13029, Q3UZD5, Q60636, Q63755, Q6P2A1, Q8BZ97, Q96EQ9, Q9CXE0, Q9GZV8, Q9H4Q4, Q9NQV8, Q9NQW5, Q9NQX0, Q9NQX1, A2AGX3, A2BID7, B4F6U4, E9Q8T2, I7HJS4, P0C6Y7, P57071, Q3UTQ7, Q5R5M1, Q5RAX9, Q80V63, Q8IZ20, Q93560, Q9NQV5, Q9NQV6, Q9NQV7, Q9QZP2, Q9UKN5, A2A935, B7ZRM8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	27
Uncertain significance	278
Likely benign	399
Benign	49

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1076993	NC_000004.11:g.(?121616266)(121720900_?)del	Pathogenic
1452157	NM_018699.4(PRDM5):c.472A>T (p.Lys158Ter)	Pathogenic
1899424	NM_018699.4(PRDM5):c.1672C>T (p.Arg558Ter)	Pathogenic
2080144	NM_018699.4(PRDM5):c.143del (p.Leu48fs)	Pathogenic
2426482	NC_000004.11:g.(?121616266)(121843763_?)del	Pathogenic
2426484	NC_000004.11:g.(?121720796)(121720920_?)del	Pathogenic
2426485	NC_000004.11:g.(?121616266)(121742520_?)del	Pathogenic
2426486	NC_000004.11:g.(?121616266)(121720920_?)del	Pathogenic
2627792	NM_018699.4(PRDM5):c.1036C>T (p.Arg346Ter)	Pathogenic
2698393	NM_018699.4(PRDM5):c.246del (p.Arg83fs)	Pathogenic
2717534	NM_018699.4(PRDM5):c.571C>T (p.Gln191Ter)	Pathogenic
2748038	NM_018699.4(PRDM5):c.893C>A (p.Ser298Ter)	Pathogenic
2788089	NM_018699.4(PRDM5):c.1132del (p.Cys378fs)	Pathogenic
2831472	NM_018699.4(PRDM5):c.1295del (p.Phe432fs)	Pathogenic
2847253	NM_018699.4(PRDM5):c.1532del (p.His511fs)	Pathogenic
2966290	NM_018699.4(PRDM5):c.1114G>T (p.Glu372Ter)	Pathogenic
31110	NM_018699.3(PRDM5):c.946_1623del	Pathogenic
31111	NM_018699.4(PRDM5):c.1768C>T (p.Arg590Ter)	Pathogenic
31112	NM_018699.4(PRDM5):c.93+1G>A	Pathogenic
31114	NM_018699.4(PRDM5):c.974del (p.Cys325fs)	Pathogenic
31115	NM_018699.4(PRDM5):c.93+2T>C	Pathogenic
3227136	NM_018699.4(PRDM5):c.1050C>A (p.Cys350Ter)	Pathogenic
3246753	NC_000004.11:g.(?121675688)(121675813_?)del	Pathogenic
3604168	NM_018699.4(PRDM5):c.1258_1259del (p.Gln420fs)	Pathogenic
3641590	NM_018699.4(PRDM5):c.503_506del (p.Ala168fs)	Pathogenic
3641721	NM_018699.4(PRDM5):c.806_834dup (p.Leu279delinsValGluArgGlyTer)	Pathogenic
3730758	NM_018699.4(PRDM5):c.338_341del (p.Ile113fs)	Pathogenic
4531924	NM_018699.4(PRDM5):c.1138_1140delinsTA (p.Leu380fs)	Pathogenic
4729934	NM_018699.4(PRDM5):c.15C>A (p.Tyr5Ter)	Pathogenic
4749945	NM_018699.4(PRDM5):c.800_806dup (p.Cys269Ter)	Pathogenic

SpliceAI

4682 predictions. Top by Δscore:

Variant	Effect	Δscore
4:120710307:A:AC	donor_gain	1.0000
4:120710308:C:CC	donor_gain	1.0000
4:120710308:CAT:C	donor_gain	1.0000
4:120710308:CATCA:C	donor_gain	1.0000
4:120754551:AC:A	donor_gain	1.0000
4:120754552:CC:C	donor_gain	1.0000
4:120781142:CTTT:C	donor_gain	1.0000
4:120784996:A:AC	donor_gain	1.0000
4:120784997:C:CC	donor_gain	1.0000
4:120799655:GTTTA:G	donor_loss	1.0000
4:120799656:TTTA:T	donor_loss	1.0000
4:120799657:TTA:T	donor_loss	1.0000
4:120799658:TA:T	donor_loss	1.0000
4:120799659:ACC:A	donor_loss	1.0000
4:120799660:C:CT	donor_loss	1.0000
4:120799741:TGAAT:T	acceptor_gain	1.0000
4:120799742:GAAT:G	acceptor_gain	1.0000
4:120799743:AAT:A	acceptor_gain	1.0000
4:120799743:AATC:A	acceptor_loss	1.0000
4:120799744:AT:A	acceptor_gain	1.0000
4:120799744:ATC:A	acceptor_loss	1.0000
4:120799745:TCT:T	acceptor_loss	1.0000
4:120799746:C:CC	acceptor_gain	1.0000
4:120799746:CTG:C	acceptor_loss	1.0000
4:120799747:T:A	acceptor_loss	1.0000
4:120799756:T:C	acceptor_gain	1.0000
4:120811364:A:AC	donor_gain	1.0000
4:120811365:C:CC	donor_gain	1.0000
4:120811366:TGA:T	donor_loss	1.0000
4:120816817:A:C	donor_gain	1.0000

AlphaMissense

4251 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:120695171:A:C	F611L	1.000
4:120695171:A:T	F611L	1.000
4:120695172:A:G	F611S	1.000
4:120695173:A:G	F611L	1.000
4:120695194:A:G	C604R	1.000
4:120695233:G:C	H591D	1.000
4:120695241:A:G	L588P	1.000
4:120695258:A:C	F582L	1.000
4:120695258:A:T	F582L	1.000
4:120695260:A:G	F582L	1.000
4:120710314:A:G	C575R	1.000
4:120710375:G:C	F554L	1.000
4:120710375:G:T	F554L	1.000
4:120710377:A:G	F554L	1.000
4:120754559:G:C	H539Q	1.000
4:120754559:G:T	H539Q	1.000
4:120754566:C:G	R537P	1.000
4:120754571:G:C	H535Q	1.000
4:120754571:G:T	H535Q	1.000
4:120754573:G:C	H535D	1.000
4:120754581:A:G	L532P	1.000
4:120754593:T:A	K528I	1.000
4:120754598:G:C	F526L	1.000
4:120754598:G:T	F526L	1.000
4:120754599:A:G	F526S	1.000
4:120754600:A:G	F526L	1.000
4:120754611:C:T	C522Y	1.000
4:120754621:A:G	C519R	1.000
4:120777192:G:C	H511Q	1.000
4:120777192:G:T	H511Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000012894 (4:120734782 G>A), RS1000022289 (4:120801941 T>C), RS1000029594 (4:120761114 G>A,T), RS1000037484 (4:120820353 T>C,G), RS1000070452 (4:120689677 G>A), RS1000079305 (4:120708726 A>C), RS1000090612 (4:120754709 C>A,T), RS1000106478 (4:120885277 T>C), RS1000109424 (4:120833427 T>C), RS1000118020 (4:120689652 G>A), RS1000147498 (4:120813108 T>A,C), RS1000148469 (4:120700627 C>A), RS1000154732 (4:120798068 C>T), RS1000170928 (4:120731678 G>A), RS1000173144 (4:120700095 G>T)

Disease associations

OMIM: gene MIM:614161 | disease phenotypes: MIM:130000, MIM:614170, MIM:180500

GenCC curated gene-disease

Disease	Classification	Inheritance
brittle cornea syndrome 2	Definitive	Autosomal recessive
brittle cornea syndrome	Supportive	Autosomal recessive
aortic disorder	Limited	Autosomal dominant
Axenfeld-Rieger syndrome	Limited	Autosomal dominant

Mondo (7): Ehlers-Danlos syndrome (MONDO:0020066), brittle cornea syndrome 2 (MONDO:0013605), Axenfeld-Rieger syndrome type 1 (MONDO:0008386), connective tissue disorder (MONDO:0003900), aortic disorder (MONDO:0005561), brittle cornea syndrome (MONDO:0009242), Axenfeld-Rieger syndrome (MONDO:0019187)

Orphanet (3): Ehlers-Danlos syndrome (Orphanet:98249), Brittle cornea syndrome (Orphanet:90354), Axenfeld-Rieger syndrome (Orphanet:782)

HPO phenotypes

45 total (30 of 45 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000365	Hearing impairment
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000485	Megalocornea
HP:0000501	Glaucoma
HP:0000541	Retinal detachment
HP:0000545	Myopia
HP:0000559	Corneal scarring
HP:0000563	Keratoconus
HP:0000572	Visual loss
HP:0000592	Blue sclerae
HP:0000647	Sclerocornea
HP:0000939	Osteoporosis
HP:0000974	Hyperextensible skin
HP:0000977	Soft skin
HP:0000978	Bruising susceptibility
HP:0001119	Keratoglobus
HP:0001131	Corneal dystrophy
HP:0001166	Arachnodactyly
HP:0001288	Gait disturbance
HP:0001319	Neonatal hypotonia
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia
HP:0001537	Umbilical hernia
HP:0001634	Mitral valve prolapse
HP:0001642	Pulmonic stenosis

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000085_1	Fasting plasma glucose	6.000000e-06
GCST000085_5	Fasting plasma glucose	5.000000e-06
GCST000982_7	F-cell distribution in sickle cell anaemia	6.000000e-06
GCST001762_584	Obesity-related traits	1.000000e-06
GCST003477_6	Monobrow thickness	4.000000e-06
GCST003773_4	Loneliness (multivariate analysis)	4.000000e-06
GCST009310_14	Sensorimotor dexterity	5.000000e-06
GCST012146_6	Hemoglobin levels	9.000000e-06
GCST012146_8	Hemoglobin levels	8.000000e-06
GCST012291_5	Schizophrenia, bipolar disorder or recurrent major depressive disorder	4.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004576	fetal hemoglobin measurement
EFO:0004338	body weight
EFO:0007865	loneliness measurement
EFO:0008354	cognitive function measurement
EFO:0004509	hemoglobin measurement
EFO:0004952	disease recurrence

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D001018	Aortic Diseases	C14.907.109
D003240	Connective Tissue Diseases	C17.300
D004535	Ehlers-Danlos Syndrome	C14.907.454.240; C15.378.463.515.240; C16.131.831.428; C16.320.850.260; C17.300.200.310; C17.800.804.428; C17.800.827.260
C535679	Axenfeld-Rieger syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression	4
Air Pollutants	increases abundance, increases expression, decreases expression	3
mercuric bromide	increases expression, affects cotreatment	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases methylation	1
methylmercuric chloride	decreases expression	1
cinnamaldehyde	increases expression	1
butyraldehyde	decreases expression	1
entinostat	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
dorsomorphin	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	affects methylation	1
Dimethyl Sulfoxide	increases expression	1
Gallic Acid	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02596048	PHASE4	COMPLETED	A Multicenter Study of Iomeron®-400 Used With Multi-detector Computed Tomography Angiography (MDCTA)
NCT05246397	PHASE4	COMPLETED	Sugammadex Titration in Cardiac Surgery Patients
NCT04890431	PHASE4	UNKNOWN	Impact of Oxygen Therapy on Fatigue in Patients With Hypermobile-type Ehlers-Danlos Syndrome
NCT05603741	PHASE4	ACTIVE_NOT_RECRUITING	Local Anesthetic Response in Ehlers-Danlos Syndrome (EDS) and Healthy Volunteers
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT05279937	PHASE3	NOT_YET_RECRUITING	The Ultrasound-Guided Dextrose Prolotherapy in Ehlers-Danlos Syndrome Patients
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00001966	PHASE2	COMPLETED	Mind-Body Therapy for Pain in Ehlers-Danlos Syndrome
NCT00004357	PHASE2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	PHASE2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	PHASE2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	PHASE2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	PHASE2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	PHASE2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	PHASE2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT01093911	PHASE1	COMPLETED	Safety Study of CDP7657 in Healthy Volunteers and Patients With Systemic Lupus Erythematosus (SLE)
NCT01764594	PHASE1	COMPLETED	Safety Study of CDP7657 in Patients With Systemic Lupus Erythematosus
NCT02392130	PHASE1	COMPLETED	A Clinical Trial to Assess the Potential of LEO 130852A Gel to Reduce Steroid Induced Skin Atrophy on Healthy Skin
NCT03337165	PHASE1	COMPLETED	Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
NCT03929120	PHASE1	COMPLETED	Allogeneic Bone Marrow Mesenchymal Stem Cells for Patients With Interstitial Lung Disease (ILD) & Connective Tissue Disorders (CTD)
NCT03610529	Not specified	UNKNOWN	CardioSenseSystem Compared Study Regarding Efficacy and Safety in the Monitoring of ECG
NCT04231461	Not specified	COMPLETED	Quality of Life After Cardiac Surgery
NCT06022653	Not specified	RECRUITING	Asan Aorta and Peripheral Registry
NCT07064460	Not specified	RECRUITING	Duke Customized Aortic Aneurysm Repair With Endovascular Stent-grafts - Duke CARES Trial