FAM193A

Summary

FAM193A (family with sequence similarity 193 member A, HGNC:16822) is a protein-coding gene on chromosome 4p16.3, encoding Protein FAM193A (P78312). Acts as a positive regulator of p53/TP53 by interacting with p53 repressors MDM2 and MDM4 and destabilizing MDM4 which leads to enhanced p53 transcriptional activity.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 193 total — 1 pathogenic
• MANE Select transcript: NM_001366318

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16822
Approved symbol	FAM193A
Name	family with sequence similarity 193 member A
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	RES4-22
Ensembl gene	ENSG00000125386
Ensembl biotype	protein_coding
OMIM	620037
Entrez	8603

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000324666, ENST00000382839, ENST00000502458, ENST00000505311, ENST00000506120, ENST00000506904, ENST00000512465, ENST00000513350, ENST00000513898, ENST00000545951, ENST00000637812, ENST00000931499, ENST00000970595, ENST00000970596, ENST00000970597

RefSeq mRNA: 6 — MANE Select: NM_001366318 NM_001256666, NM_001256667, NM_001256668, NM_001366316, NM_001366318, NM_003704

CCDS: CCDS33943, CCDS58874, CCDS58875, CCDS58876, CCDS93467

Canonical transcript exons

ENST00000637812 — 21 exons

Exon	Start	End
ENSE00000854795	2639735	2639859
ENSE00000854806	2659558	2659670
ENSE00000854811	2659812	2660054
ENSE00000854812	2662838	2662991
ENSE00000854819	2663109	2663288
ENSE00000854823	2672121	2672372
ENSE00001080016	2690698	2690970
ENSE00001080019	2694946	2695129
ENSE00001080022	2689506	2689704
ENSE00001164061	2646685	2646832
ENSE00001266537	2693586	2693874
ENSE00002073430	2630935	2631169
ENSE00002084936	2625262	2625395
ENSE00003478727	2716023	2716104
ENSE00003658596	2699680	2700544
ENSE00003677360	2696363	2696593
ENSE00003756635	2657803	2657880
ENSE00003792978	2596084	2596329
ENSE00003794990	2626410	2626577
ENSE00003795065	2536647	2537170
ENSE00003800235	2731775	2732573

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 94.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.3501 / max 339.1804, expressed in 1816 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46620	25.1723	1816
46619	0.1778	69

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	94.77	gold quality
ventricular zone	UBERON:0003053	90.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.70	gold quality
cortical plate	UBERON:0005343	89.06	gold quality
oocyte	CL:0000023	88.02	gold quality
ganglionic eminence	UBERON:0004023	87.67	gold quality
embryo	UBERON:0000922	87.45	gold quality
secondary oocyte	CL:0000655	87.07	gold quality
calcaneal tendon	UBERON:0003701	86.84	gold quality
cartilage tissue	UBERON:0002418	86.07	gold quality
right testis	UBERON:0004534	85.66	gold quality
tibialis anterior	UBERON:0001385	85.62	silver quality
left testis	UBERON:0004533	85.49	gold quality
testis	UBERON:0000473	85.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.32	gold quality
cerebellar hemisphere	UBERON:0002245	85.29	gold quality
cerebellar cortex	UBERON:0002129	85.27	gold quality
tendon	UBERON:0000043	85.26	gold quality
ileal mucosa	UBERON:0000331	85.25	gold quality
cerebellum	UBERON:0002037	84.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.72	gold quality
gastrocnemius	UBERON:0001388	84.65	gold quality
muscle of leg	UBERON:0001383	84.56	gold quality
body of uterus	UBERON:0009853	84.04	gold quality
popliteal artery	UBERON:0002250	83.85	gold quality
tibial artery	UBERON:0007610	83.85	gold quality
pituitary gland	UBERON:0000007	83.79	gold quality
stromal cell of endometrium	CL:0002255	83.74	gold quality
adult organism	UBERON:0007023	83.70	gold quality
left ovary	UBERON:0002119	83.65	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.73
E-MTAB-7381	no	471.62
E-MTAB-7303	no	374.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting FAM193A, 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-6798-5P	100.00	65.77	699
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-936	98.87	70.51	1124
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-1537-5P	98.70	68.33	999
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-3691-5P	98.62	65.88	552
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-4718	98.55	68.61	814
HSA-MIR-499B-5P	98.35	68.39	988

Literature-anchored findings (GeneRIF, showing 1)

• FAM193A is a positive regulator of p53 activity. (PMID:36897777)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam193a	ENSDARG00000102787
mus_musculus	Fam193a	ENSMUSG00000037210
rattus_norvegicus	Fam193a	ENSRNOG00000013832
drosophila_melanogaster	CG7518	FBGN0038108

Paralogs (1): FAM193B (ENSG00000146067)

Protein

Protein identifiers

Protein FAM193A — P78312 (reviewed: P78312)

Alternative names: Protein IT14

All UniProt accessions (4): P78312, A0A1B0GVL4, D6RFZ4, E7EUR8

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a positive regulator of p53/TP53 by interacting with p53 repressors MDM2 and MDM4 and destabilizing MDM4 which leads to enhanced p53 transcriptional activity.

Subunit / interactions. Component of a ternary complex composed of FAM193A, MDM4 and MDM2; interaction of FAM193A with MDM4 is mediated by the MDM4 RING-type zinc finger and results in MDM4 destabilization. Although FAM193A interacts with MDM4 and MDM2, it does not affect formation of the p53-MDM2-MDM4 transcriptional repressor complex.

Subcellular location. Nucleus. Cytoplasm.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the FAM193 family.

Isoforms (7)

UniProt ID	Names	Canonical?
P78312-7	1	yes
P78312-1	2, RES4-22B
P78312-2	3, RES4-22A
P78312-3	4, RES4-22C
P78312-4	5, RES4-22D
P78312-5	6
P78312-6	7

RefSeq proteins (6): NP_001243595, NP_001243596, NP_001243597, NP_001353245, NP_001353247, NP_003695 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029717	FAM193	Family
IPR031802	FAM193_C	Domain

Pfam: PF15914

UniProt features (38 total): compositionally biased region 10, splice variant 9, region of interest 8, modified residue 5, coiled-coil region 3, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78312-F1	51.17	0.08

Functional residue map

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

Post-translational modifications (5): 584, 674, 933, 1420, 1435

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 85 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, HSIAO_HOUSEKEEPING_GENES, CAGCTG_AP4_Q5, GOBP_POSITIVE_REGULATION_OF_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, ONKEN_UVEAL_MELANOMA_UP, NF1_Q6_01, BLALOCK_ALZHEIMERS_DISEASE_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_TTD_DN, chr4p16, GOBP_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_REGULATION_OF_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, LXR_Q3

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

14 interactions, top by confidence:

A	B	Type	Score
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
H3C13	FAM193A	psi-mi:“MI:0915”(physical association)	0.400
FAM193A	TCOF1	psi-mi:“MI:0915”(physical association)	0.400
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
FGF11	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
SYCE1	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
MDM4	TP73	psi-mi:“MI:0914”(association)	0.350
MAGEA10	KANSL1L	psi-mi:“MI:0914”(association)	0.350
AGGF1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
SRSF7	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
ANKRD28	TBKBP1	psi-mi:“MI:2364”(proximity)	0.270
	FAM193A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (82): FAM193A (Affinity Capture-MS), FAM193A (Affinity Capture-MS), FAM193A (Affinity Capture-RNA), FAM193A (Affinity Capture-MS), FAM193A (Affinity Capture-MS), FAM193A (Affinity Capture-RNA), TCOF1 (Proximity Label-MS), FAM193A (Proximity Label-MS), FAM193A (Proximity Label-MS), FAM193A (Proximity Label-MS), FAM193A (Proximity Label-MS), FAM193A (Proximity Label-MS), FAM193A (Proximity Label-MS), FAM193A (Proximity Label-MS), FAM193A (Proximity Label-MS)

ESM2 similar proteins: A0JLT2, A4QNZ7, A5PK23, B1AZP2, F5HSE3, O60293, O75420, O95402, P61129, P78312, P97839, Q03111, Q07FY3, Q08C81, Q08DM1, Q174D3, Q1LVC2, Q32NP7, Q3T044, Q4G0F8, Q5EAY2, Q5F368, Q5R8Q8, Q5U2R6, Q6DD45, Q6DRL8, Q6PEI3, Q7TN02, Q80Z38, Q8C1B1, Q8C1S0, Q8CFT2, Q8CGI1, Q8IVL1, Q8K4J6, Q90YL3, Q90YY5, Q969V6, Q96A73, Q99MR1

Diamond homologs: A7MB40, P78312, Q3U2K0, Q8CGI1, Q96PV7, Q09FC8, Q5H9K5, Q68CZ1, Q8N9N2, Q8TDM0, Q96J02, Q96MD7, A0A096LPI5, A2RRD8, A6NHJ4, A6NJG6, P0CJ79, P17035, P51522, P51957, Q08AN1, Q0VGE8, Q3MIS6, Q5HY98, Q5R8X1, Q5RER9, Q5VIY5, Q6PDB4, Q6ZN06, Q6ZN19, Q6ZNA1, Q6ZNG1, Q76KX8, Q7L2R6, Q86XN6, Q86XU0, Q8N4W9, Q8N782, Q8N823, Q8N8H1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	160
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
814518	GRCh37/hg19 4p16.3(chr4:68345-2786584)x1	Pathogenic

SpliceAI

4623 predictions. Top by Δscore:

Variant	Effect	Δscore
4:2626408:A:AG	acceptor_gain	1.0000
4:2626409:G:GG	acceptor_gain	1.0000
4:2626409:GA:G	acceptor_gain	1.0000
4:2626409:GAGA:G	acceptor_gain	1.0000
4:2626409:GAGAA:G	acceptor_gain	1.0000
4:2626552:G:GT	donor_gain	1.0000
4:2626555:G:GT	donor_gain	1.0000
4:2626573:GA:G	donor_gain	1.0000
4:2626574:A:G	donor_gain	1.0000
4:2626574:ATAGG:A	donor_loss	1.0000
4:2626575:TAGG:T	donor_loss	1.0000
4:2626576:AGGTA:A	donor_loss	1.0000
4:2626579:T:G	donor_loss	1.0000
4:2630933:A:AG	acceptor_gain	1.0000
4:2630934:G:GG	acceptor_gain	1.0000
4:2631166:TCTGG:T	donor_loss	1.0000
4:2631167:CTGG:C	donor_loss	1.0000
4:2631168:TGGT:T	donor_loss	1.0000
4:2631169:GGT:G	donor_loss	1.0000
4:2631170:G:GG	donor_gain	1.0000
4:2631170:GTAA:G	donor_loss	1.0000
4:2631171:T:G	donor_loss	1.0000
4:2638280:G:GT	donor_gain	1.0000
4:2639719:A:AG	acceptor_gain	1.0000
4:2639734:GGA:G	acceptor_gain	1.0000
4:2639856:TCAGG:T	donor_loss	1.0000
4:2639857:CAGG:C	donor_loss	1.0000
4:2639858:AGG:A	donor_loss	1.0000
4:2639859:GGTA:G	donor_loss	1.0000
4:2639860:GT:G	donor_loss	1.0000

AlphaMissense

10025 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:2639768:T:A	W67R	1.000
4:2639768:T:C	W67R	1.000
4:2659852:T:C	C224R	1.000
4:2695091:T:A	C789S	1.000
4:2695091:T:C	C789R	1.000
4:2695092:G:A	C789Y	1.000
4:2695092:G:C	C789S	1.000
4:2695092:G:T	C789F	1.000
4:2695093:C:G	C789W	1.000
4:2695097:T:A	C791S	1.000
4:2695097:T:C	C791R	1.000
4:2695098:G:A	C791Y	1.000
4:2695098:G:C	C791S	1.000
4:2695099:C:G	C791W	1.000
4:2695100:T:C	C792R	1.000
4:2695101:G:A	C792Y	1.000
4:2695102:C:G	C792W	1.000
4:2695106:T:A	C794S	1.000
4:2695106:T:C	C794R	1.000
4:2695107:G:A	C794Y	1.000
4:2695107:G:C	C794S	1.000
4:2695107:G:T	C794F	1.000
4:2695108:C:G	C794W	1.000
4:2695112:T:C	F796L	1.000
4:2695114:C:A	F796L	1.000
4:2695114:C:G	F796L	1.000
4:2695115:T:C	F797L	1.000
4:2695116:T:G	F797C	1.000
4:2695117:T:A	F797L	1.000
4:2695117:T:G	F797L	1.000

dbSNP variants (sampled 300 via entrez): RS1000055890 (4:2566417 C>T), RS1000071833 (4:2540720 G>A), RS1000101762 (4:2652139 C>G), RS1000106789 (4:2581675 T>C), RS1000107258 (4:2618911 T>C), RS1000110632 (4:2641601 G>A), RS1000111842 (4:2723779 G>A), RS1000114622 (4:2718634 G>A), RS1000137275 (4:2640177 A>G), RS1000141798 (4:2689045 A>G), RS1000145079 (4:2713415 A>G), RS1000156675 (4:2610662 C>A), RS1000181737 (4:2602667 T>C), RS1000223402 (4:2567139 G>A), RS1000225100 (4:2537551 C>A,G,T)

Disease associations

OMIM: gene MIM:620037 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST005141_49	Cognitive ability (MTAG)	4.000000e-08
GCST005142_51	Cognitive ability	2.000000e-06
GCST005316_147	Intelligence (MTAG)	7.000000e-10
GCST005759_7	Dimensional psychopathology (Social)	4.000000e-07
GCST006269_698	General cognitive ability	1.000000e-09
GCST006624_120	Systolic blood pressure	5.000000e-18
GCST007267_44	Systolic blood pressure	1.000000e-14
GCST007269_34	Pulse pressure	1.000000e-12
GCST007576_220	Chronotype	2.000000e-08
GCST009508_1	Diastolic blood pressure	9.000000e-07
GCST011956_79	Systemic lupus erythematosus	1.000000e-08
GCST90002382_590	Eosinophil percentage of white cells	3.000000e-10

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0009100	social domain measurement
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0008328	chronotype measurement
EFO:0006336	diastolic blood pressure
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
Cisplatin	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	decreases methylation	1
butyraldehyde	decreases expression	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Leflunomide	increases expression	1
Acrolein	increases expression, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Quercetin	increases expression	1
Ribonucleotides	affects binding	1
Dihydrotestosterone	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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