FAM199X

Summary

FAM199X (family with sequence similarity 199, X-linked, HGNC:25195) is a protein-coding gene on chromosome Xq22.2, encoding Protein FAM199X (Q6PEV8).

At a glance

• Clinical variants (ClinVar): 78 total — 2 pathogenic
• MANE Select transcript: NM_207318

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25195
Approved symbol	FAM199X
Name	family with sequence similarity 199, X-linked
Location	Xq22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000123575
Ensembl biotype	protein_coding
Entrez	139231

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000299906, ENST00000493442, ENST00000878950, ENST00000878951, ENST00000878952, ENST00000957125

RefSeq mRNA: 1 — MANE Select: NM_207318 NM_207318

CCDS: CCDS35364

Canonical transcript exons

ENST00000493442 — 6 exons

Exon	Start	End
ENSE00001154767	104188040	104188306
ENSE00001154779	104186066	104186215
ENSE00001165820	104166453	104166982
ENSE00001261495	104175623	104175842
ENSE00001952896	104189608	104195902
ENSE00003574681	104186460	104186621

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 97.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.4105 / max 101.9645, expressed in 1799 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197133	9.0590	1764
197130	4.3528	1585
197132	1.2393	821
197129	1.0360	576
197131	0.7234	434

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	97.58	gold quality
corpus epididymis	UBERON:0004359	97.51	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.10	gold quality
substantia nigra pars compacta	UBERON:0001965	96.94	gold quality
oocyte	CL:0000023	96.68	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.62	gold quality
secondary oocyte	CL:0000655	96.55	gold quality
epithelial cell of pancreas	CL:0000083	96.31	gold quality
lateral globus pallidus	UBERON:0002476	96.23	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.96	gold quality
superior vestibular nucleus	UBERON:0007227	95.88	gold quality
medulla oblongata	UBERON:0001896	95.65	gold quality
dorsal plus ventral thalamus	UBERON:0001897	95.53	gold quality
caput epididymis	UBERON:0004358	95.49	gold quality
subthalamic nucleus	UBERON:0001906	95.30	gold quality
ventral tegmental area	UBERON:0002691	95.06	gold quality
pons	UBERON:0000988	95.05	gold quality
globus pallidus	UBERON:0001875	94.73	gold quality
seminal vesicle	UBERON:0000998	94.48	gold quality
medial globus pallidus	UBERON:0002477	94.42	gold quality
inferior vagus X ganglion	UBERON:0005363	94.37	gold quality
parietal lobe	UBERON:0001872	94.30	gold quality
postcentral gyrus	UBERON:0002581	94.18	gold quality
entorhinal cortex	UBERON:0002728	94.02	gold quality
superior frontal gyrus	UBERON:0002661	93.53	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.47	gold quality
endothelial cell	CL:0000115	93.28	silver quality
trigeminal ganglion	UBERON:0001675	92.75	gold quality
upper arm skin	UBERON:0004263	92.70	gold quality
kidney epithelium	UBERON:0004819	92.66	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	71.07
E-ANND-3	no	4.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

329 targeting FAM199X, 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-3646	100.00	73.56	5283
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
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-340-5P	100.00	72.50	4437
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-3P	99.99	70.75	2484

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam199x	ENSDARG00000009982
mus_musculus	Fam199x	ENSMUSG00000042595
rattus_norvegicus	Fam199x	ENSRNOG00000078832

Protein

Protein identifiers

Protein FAM199X — Q6PEV8 (reviewed: Q6PEV8)

All UniProt accessions (2): B0QYU2, Q6PEV8

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the FAM199 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6PEV8-1	1	yes
Q6PEV8-2	2

RefSeq proteins (1): NP_997201* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029672	FAM199X_fam	Family

Pfam: PF15814

UniProt features (7 total): compositionally biased region 2, modified residue 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PEV8-F1	57.50	0.01

Functional residue map

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

Post-translational modifications (2): 316, 321

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 161 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, LIAO_METASTASIS, DOUGLAS_BMI1_TARGETS_DN, COATES_MACROPHAGE_M1_VS_M2_DN, ZHANG_BREAST_CANCER_PROGENITORS_UP, MODULE_48, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, MODULE_95, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, KONDO_PROSTATE_CANCER_HCP_WITH_H3K27ME3, GEORGES_TARGETS_OF_MIR192_AND_MIR215, HOELZEL_NF1_TARGETS_UP, PHESSE_TARGETS_OF_APC_AND_MBD2_DN, chrXq22

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

530 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM199X	FANK1	Q8TC84	591
FAM199X	DHX32	Q7L7V1	580
FAM199X	ZNF717	Q9BY31	578
FAM199X	ZNF595	Q8IYB9	522
FAM199X	GCNT2	Q8N0V5	508
FAM199X	BIVM	Q86UB2	507
FAM199X	PROSER2	Q86WR7	451
FAM199X	CSRNP2	Q9H175	447
FAM199X	HROB	Q8N3J3	447
FAM199X	NEU4	Q8WWR8	415
FAM199X	ARHGEF10	O15013	407
FAM199X	TCERG1L	Q5VWI1	398
FAM199X	IL1RAPL1	Q9NZN1	398
FAM199X	FBXL16	Q8N461	396
FAM199X	NGEF	Q8N5V2	395

IntAct

28 interactions, top by confidence:

A	B	Type	Score
WDR5	KMT2D	psi-mi:“MI:0914”(association)	0.910
CSNK1E	PER2	psi-mi:“MI:0914”(association)	0.850
CSNK1D	PER2	psi-mi:“MI:0914”(association)	0.810
WDR5	FAM199X	psi-mi:“MI:0915”(physical association)	0.740
WDR5	MEN1	psi-mi:“MI:0914”(association)	0.710
CSNK1E	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
CSNK1E	POTEF	psi-mi:“MI:0914”(association)	0.530
ERMAP	AP3B1	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
FAM199X	OCIAD2	psi-mi:“MI:0915”(physical association)	0.400
DCLRE1B	FSBP	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M	CENPB	psi-mi:“MI:0914”(association)	0.350
CSNK1D	TMEM131L	psi-mi:“MI:0914”(association)	0.350
Paxip1	CDC27	psi-mi:“MI:0914”(association)	0.350
ZFP57	PPM1G	psi-mi:“MI:0914”(association)	0.350
ZNF627	POLR1C	psi-mi:“MI:0914”(association)	0.350
MBIP	CIBAR1	psi-mi:“MI:0914”(association)	0.350
GOLGA8G	GOLGA8J	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
C21orf58	MTA2	psi-mi:“MI:0914”(association)	0.350
RPL37A	NKRF	psi-mi:“MI:0914”(association)	0.350
CEP128	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
WDR5	FAM199X	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (37): FAM199X (Affinity Capture-MS), FAM199X (Affinity Capture-MS), FAM199X (Affinity Capture-MS), FAM199X (Affinity Capture-MS), FAM199X (Proximity Label-MS), FAM199X (Affinity Capture-MS), FAM199X (Affinity Capture-MS), FAM199X (Affinity Capture-MS), FAM199X (Affinity Capture-MS), FAM199X (Affinity Capture-MS), FAM199X (Affinity Capture-MS), FAM199X (Affinity Capture-MS), FAM199X (Affinity Capture-MS), FAM199X (Affinity Capture-MS), WDR5 (Two-hybrid)

ESM2 similar proteins: A0A140LFM6, A0A2K1J5A5, A0A2K1JJ00, A0JMD2, A2BIL8, A4IGV6, A6NKB5, B0S728, B3DHS1, C5DZR8, F1QPR4, F1QR98, O44535, O70343, P0CAX8, Q0P4S0, Q149F5, Q1LV19, Q1RMQ5, Q28J76, Q3ZBS1, Q4V7H1, Q5DU28, Q5REU9, Q5ZM13, Q62417, Q641I1, Q6AXJ7, Q6DDX3, Q6DFB0, Q6GP60, Q6NWJ0, Q6P5X7, Q6P6I6, Q6P9N1, Q6PEV8, Q7T346, Q80W69, Q865B7, Q8BLN6

Diamond homologs: Q28J76, Q6AXJ7, Q6DDX3, Q6GP60, Q6PEV8, Q8K2D0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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
Epigenetic regulation of gene expression	5	19.8×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	17
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
11078	NC_000023.11:g.(?103776506)(103799000_104817980)del	Pathogenic
691849	GRCh37/hg19 Xq22.1-22.3(chrX:101029649-106702784)x1	Pathogenic

SpliceAI

1482 predictions. Top by Δscore:

Variant	Effect	Δscore
X:104166979:ACAGG:A	donor_loss	1.0000
X:104166980:CAGGT:C	donor_loss	1.0000
X:104166981:AGGTA:A	donor_loss	1.0000
X:104166982:GGTAC:G	donor_loss	1.0000
X:104166983:G:C	donor_loss	1.0000
X:104166984:T:G	donor_loss	1.0000
X:104175769:G:T	donor_gain	1.0000
X:104184291:T:TA	acceptor_gain	1.0000
X:104186061:T:G	acceptor_gain	1.0000
X:104186062:A:AG	acceptor_gain	1.0000
X:104186063:A:G	acceptor_gain	1.0000
X:104186064:A:AG	acceptor_gain	1.0000
X:104186065:G:GG	acceptor_gain	1.0000
X:104186120:A:AG	acceptor_gain	1.0000
X:104186121:G:GG	acceptor_gain	1.0000
X:104186456:ATAGG:A	acceptor_loss	1.0000
X:104186457:T:G	acceptor_gain	1.0000
X:104186457:TAGGT:T	acceptor_loss	1.0000
X:104186458:A:T	acceptor_loss	1.0000
X:104186568:GACA:G	donor_gain	1.0000
X:104186572:G:GG	donor_gain	1.0000
X:104186618:GCAG:G	donor_gain	1.0000
X:104186620:AG:A	donor_loss	1.0000
X:104186621:GG:G	donor_loss	1.0000
X:104186623:T:A	donor_loss	1.0000
X:104188307:G:GG	donor_gain	1.0000
X:104189607:GAA:G	acceptor_gain	1.0000
X:104189743:G:GT	donor_gain	1.0000
X:104189752:G:GT	donor_gain	1.0000
X:104189768:TTTTG:T	donor_gain	1.0000

AlphaMissense

2597 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:104186189:T:A	W181R	1.000
X:104186189:T:C	W181R	1.000
X:104186190:G:C	W181S	1.000
X:104186191:G:C	W181C	1.000
X:104186191:G:T	W181C	1.000
X:104186470:T:A	I193N	1.000
X:104186479:T:C	L196P	1.000
X:104186481:A:C	S197R	1.000
X:104186483:T:A	S197R	1.000
X:104186483:T:G	S197R	1.000
X:104186519:A:C	Q209H	1.000
X:104186519:A:T	Q209H	1.000
X:104186521:T:C	L210P	1.000
X:104186527:T:A	I212N	1.000
X:104186527:T:G	I212S	1.000
X:104186530:T:A	I213N	1.000
X:104186530:T:C	I213T	1.000
X:104186530:T:G	I213S	1.000
X:104186539:T:A	I216N	1.000
X:104186551:C:A	A220D	1.000
X:104186557:T:G	I222S	1.000
X:104186577:T:C	F229L	1.000
X:104186578:T:C	F229S	1.000
X:104186578:T:G	F229C	1.000
X:104186579:T:A	F229L	1.000
X:104186579:T:G	F229L	1.000
X:104186584:T:A	I231N	1.000
X:104186584:T:G	I231S	1.000
X:104186599:T:A	L236H	1.000
X:104186599:T:C	L236P	1.000

dbSNP variants (sampled 300 via entrez): RS1000174740 (X:104164540 C>G), RS1000358771 (X:104190497 G>A), RS1000476025 (X:104161609 G>A), RS1000536481 (X:104162691 A>T), RS1000708333 (X:104188744 T>G), RS1001152285 (X:104189925 G>A), RS1001360645 (X:104181392 G>A), RS1001393701 (X:104171134 A>G), RS1001667735 (X:104180958 G>A), RS1001771911 (X:104189277 A>G), RS1002156076 (X:104187295 G>A), RS1002275477 (X:104161521 C>G,T), RS1002652338 (X:104161057 A>G), RS1003189611 (X:104185758 C>T), RS1003224803 (X:104177062 G>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:312080

GenCC curated gene-disease

Mondo (1): Pelizaeus-Merzbacher spectrum disorder (MONDO:0010714)

Orphanet (1): Pelizaeus-Merzbacher disease (Orphanet:702)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020371	Pelizaeus-Merzbacher Disease	C10.228.140.163.100.362.775; C10.228.140.695.625.775; C10.314.400.775; C16.320.322.906; C16.320.565.189.362.775; C18.452.132.100.362.775; C18.452.648.189.362.775

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	affects cotreatment, affects expression, increases expression	5
bisphenol A	affects cotreatment, increases expression, increases methylation	2
bisphenol F	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression, increases expression	1
triphenyl phosphate	affects expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, affects expression	1
dorsomorphin	affects cotreatment, affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	affects expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Testosterone	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07382739	PHASE2	RECRUITING	A Phase 2 Study of Radiotherapy-induced Immune Priming to Enhance Elranatamab (Elra) in Relapsed Refractory Multiple Myeloma (RRMM) With Extramedullary Disease (EMD) and Paramedullary Disease (PMD) PRIME-EMD-PMD
NCT01005004	PHASE1	COMPLETED	Study of Human Central Nervous System (CNS) Stem Cells Transplantation in Pelizaeus-Merzbacher Disease (PMD) Subjects
NCT02254863	PHASE1	RECRUITING	UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells
NCT06150716	PHASE1	RECRUITING	Orbit Study: A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Intrathecally Administered ION356 in Participants With Pelizaeus Merzbacher Disease (PMD)
NCT01391637	Not specified	COMPLETED	Long-Term Follow-Up Study of Human Stem Cells Transplanted in Subjects With Connatal Pelizaeus-Merzbacher Disease (PMD)
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT05659901	Not specified	RECRUITING	Rocket Study: A Study to Characterize Biomarkers and Disease Progression in Participants With Pelizaeus-Merzbacher Disease