FAM221B

Summary

FAM221B (family with sequence similarity 221 member B, HGNC:30762) is a protein-coding gene on chromosome 9p13.3, encoding Protein FAM221B (A6H8Z2).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_001012446

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30762
Approved symbol	FAM221B
Name	family with sequence similarity 221 member B
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204930
Ensembl biotype	protein_coding
Entrez	392307

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000377984, ENST00000388950, ENST00000423537, ENST00000472182

RefSeq mRNA: 1 — MANE Select: NM_001012446 NM_001012446

CCDS: CCDS43799

Canonical transcript exons

ENST00000423537 — 7 exons

Exon	Start	End
ENSE00001504486	35825230	35825373
ENSE00001504487	35825564	35826161
ENSE00001839847	35816391	35818506
ENSE00001916764	35828463	35828732
ENSE00003522049	35819890	35820000
ENSE00003564168	35818890	35819009
ENSE00003688702	35819197	35819394

Expression profiles

Bgee: expression breadth broad, 87 present calls, max score 83.89.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0309 / max 23.0053, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100666	0.0309	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	83.89	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.85	gold quality
left testis	UBERON:0004533	79.53	gold quality
testis	UBERON:0000473	78.96	gold quality
right testis	UBERON:0004534	78.58	gold quality
quadriceps femoris	UBERON:0001377	66.43	gold quality
cerebellar vermis	UBERON:0004720	64.61	gold quality
right uterine tube	UBERON:0001302	60.77	gold quality
granulocyte	CL:0000094	58.81	gold quality
saliva-secreting gland	UBERON:0001044	55.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	55.57	gold quality
minor salivary gland	UBERON:0001830	55.52	gold quality
bone marrow	UBERON:0002371	54.23	gold quality
prostate gland	UBERON:0002367	53.52	gold quality
rectum	UBERON:0001052	53.22	gold quality
mucosa of stomach	UBERON:0001199	52.16	gold quality
monocyte	CL:0000576	52.08	gold quality
colonic epithelium	UBERON:0000397	51.90	gold quality
leukocyte	CL:0000738	51.85	gold quality
skeletal muscle tissue	UBERON:0001134	51.56	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	51.21	silver quality
sural nerve	UBERON:0015488	50.40	gold quality
muscle tissue	UBERON:0002385	49.90	silver quality
spinal cord	UBERON:0002240	48.85	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	48.76	gold quality
primary visual cortex	UBERON:0002436	48.57	silver quality
cortical plate	UBERON:0005343	48.36	silver quality
body of stomach	UBERON:0001161	46.88	gold quality
urinary bladder	UBERON:0001255	46.36	gold quality
stomach	UBERON:0000945	46.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting FAM221B, 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-574-5P	100.00	66.01	989
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-330-5P	98.73	67.63	1788

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fam221b	ENSMUSG00000043633
rattus_norvegicus	Fam221b	ENSRNOG00000025453

Paralogs (1): FAM221A (ENSG00000188732)

Protein

Protein identifiers

Protein FAM221B — A6H8Z2 (reviewed: A6H8Z2)

All UniProt accessions (3): A6H8Z2, C9JPK8, F8W8N9

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the FAM221 family.

Isoforms (3)

UniProt ID	Names	Canonical?
A6H8Z2-1	1	yes
A6H8Z2-2	2
A6H8Z2-3	3

RefSeq proteins (1): NP_001012448* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026755	Fam221a/b	Family

Pfam: PF14753

UniProt features (12 total): splice variant 4, compositionally biased region 3, region of interest 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6H8Z2-F1	64.61	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): chr9p13, NKX2_3_TARGET_GENES, ZNF223_TARGET_GENES, GSE10239_MEMORY_VS_KLRG1INT_EFF_CD8_TCELL_DN, MIR4766_5P, MIR1236_3P, MIR597_3P, GSE11924_TH1_VS_TH2_CD4_TCELL_UP, MIR6748_3P, MIR574_5P, MIR3189_5P, HAY_BONE_MARROW_DENDRITIC_CELL, DESCARTES_FETAL_LUNG_CILIATED_EPITHELIAL_CELLS, DESCARTES_FETAL_PANCREAS_MYELOID_CELLS, GSE2706_R848_VS_LPS_8H_STIM_DC_UP

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

180 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM221B	TMEM202	A6NGA9	646
FAM221B	C7orf57	Q8NEG2	527
FAM221B	FNDC8	Q8TC99	478
FAM221B	CABCOCO1	Q8IVU9	474
FAM221B	SPAAR	A0A1B0GVQ0	446
FAM221B	SPAG8	Q99932	433
FAM221B	SMIM33	A0A1B0GW64	417
FAM221B	TMEM8B	A6NDV4	415
FAM221B	BPIFA3	Q9BQP9	406
FAM221B	RNF38	Q9H0F5	374
FAM221B	RNF17	Q9BXT8	360
FAM221B	SCP2D1	Q9UJQ7	356
FAM221B	TEX13A	Q9BXU3	336
FAM221B	NPR2	P20594	312
FAM221B	SCN7A	Q01118	311

IntAct

46 interactions, top by confidence:

A	B	Type	Score
SELENOO	FAM221B	psi-mi:“MI:0915”(physical association)	0.670
	FAM221B	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	PLSCR2	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	EFHC2	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	LBX1	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	KRT35	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	CYSRT1	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	ANKRD11	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	TRIM50	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	GSC2	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	CCDC13	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	KPRP	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	ATG13	psi-mi:“MI:0914”(association)	0.350
FAM221B		psi-mi:“MI:0915”(physical association)	0.000
FAM221B	LCE2C	psi-mi:“MI:0915”(physical association)	0.000
FAM221B	PLSCR2	psi-mi:“MI:0915”(physical association)	0.000
FAM221B	EFHC2	psi-mi:“MI:0915”(physical association)	0.000
FAM221B	KPRP	psi-mi:“MI:0915”(physical association)	0.000
FAM221B	KRT35	psi-mi:“MI:0915”(physical association)	0.000
FAM221B	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
FAM221B	LZTS2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): RB1CC1 (Affinity Capture-MS), SMG6 (Affinity Capture-MS), ATG13 (Affinity Capture-MS), SELO (Affinity Capture-MS), EFNB3 (Affinity Capture-MS), ATG101 (Affinity Capture-MS), TSC2 (Affinity Capture-MS), FAM221B (Two-hybrid), FAM221B (Two-hybrid), FAM221B (Two-hybrid), FAM221B (Two-hybrid), FAM221B (Two-hybrid), FAM221B (Two-hybrid), FAM221B (Two-hybrid), FAM221B (Two-hybrid)

ESM2 similar proteins: A2VCV0, A6H8Z2, A8T6P4, C3VD30, F6QRE9, P23497, P23804, P56950, Q00987, Q0P6D6, Q13342, Q1XFL1, Q32MH5, Q4JF29, Q5BLK4, Q5PQX1, Q5VYS8, Q5ZI58, Q60524, Q62187, Q66HD8, Q68FE6, Q69ZK7, Q6DRC5, Q6IE24, Q6NYJ3, Q6P752, Q6PCX9, Q70EL1, Q76N89, Q7L190, Q7T3T8, Q7T3T9, Q7YRZ8, Q7ZUW7, Q80UF7, Q8BL06, Q8BYU6, Q8C627, Q8C9M2

Diamond homologs: A6H8Z2, Q28J59, Q2VPL9, Q66HD8, Q8C627, A4D161, Q4V8D7, Q8C790

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

912 predictions. Top by Δscore:

Variant	Effect	Δscore
9:35818900:T:TA	donor_gain	1.0000
9:35818903:T:TA	donor_gain	0.9900
9:35819006:CAGC:C	acceptor_gain	0.9900
9:35828461:AC:A	donor_gain	0.9900
9:35828462:CC:C	donor_gain	0.9900
9:35828462:CCCT:C	donor_gain	0.9900
9:35818884:CCTCA:C	donor_loss	0.9800
9:35818885:CTCAC:C	donor_loss	0.9800
9:35818886:T:TC	donor_loss	0.9800
9:35818887:C:CC	donor_loss	0.9800
9:35818888:A:AG	donor_loss	0.9800
9:35818889:C:CA	donor_loss	0.9800
9:35819011:T:A	acceptor_loss	0.9800
9:35819390:TATGT:T	acceptor_gain	0.9800
9:35819392:TGT:T	acceptor_gain	0.9800
9:35819395:C:CC	acceptor_gain	0.9800
9:35819403:T:TC	acceptor_gain	0.9800
9:35819997:AGACC:A	acceptor_loss	0.9800
9:35819998:GACCT:G	acceptor_loss	0.9800
9:35819999:ACC:A	acceptor_loss	0.9800
9:35820000:CCTA:C	acceptor_loss	0.9800
9:35820001:C:CA	acceptor_loss	0.9800
9:35820002:T:A	acceptor_loss	0.9800
9:35818638:T:C	donor_gain	0.9700
9:35818888:A:AC	donor_gain	0.9700
9:35818889:C:CC	donor_gain	0.9700
9:35818889:CCG:C	donor_gain	0.9700
9:35818969:C:CT	acceptor_gain	0.9700
9:35819010:C:CC	acceptor_gain	0.9700
9:35819021:G:GC	acceptor_gain	0.9700

AlphaMissense

2643 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:35818978:G:C	F361L	0.995
9:35818978:G:T	F361L	0.995
9:35818980:A:G	F361L	0.995
9:35819342:A:C	F302L	0.995
9:35819342:A:T	F302L	0.995
9:35819344:A:G	F302L	0.995
9:35819348:G:C	F300L	0.995
9:35819348:G:T	F300L	0.995
9:35819350:A:G	F300L	0.995
9:35818951:C:A	W370C	0.994
9:35818951:C:G	W370C	0.994
9:35818990:A:C	F357L	0.994
9:35818990:A:T	F357L	0.994
9:35818992:A:G	F357L	0.994
9:35819270:C:A	W326C	0.994
9:35819270:C:G	W326C	0.994
9:35819272:A:G	W326R	0.994
9:35819272:A:T	W326R	0.994
9:35818953:A:G	W370R	0.993
9:35818953:A:T	W370R	0.993
9:35819285:A:C	F321L	0.993
9:35819285:A:T	F321L	0.993
9:35819287:A:G	F321L	0.993
9:35819927:A:C	F272L	0.993
9:35819927:A:T	F272L	0.993
9:35819929:A:G	F272L	0.993
9:35819984:C:A	W253C	0.992
9:35819984:C:G	W253C	0.992
9:35819986:A:G	W253R	0.992
9:35819986:A:T	W253R	0.992

dbSNP variants (sampled 300 via entrez): RS1000561440 (9:35818575 C>A,T), RS1000586371 (9:35824822 C>G,T), RS1000681310 (9:35824479 C>T), RS1000934989 (9:35818230 A>G), RS1001392684 (9:35826454 T>C), RS1001508162 (9:35816446 T>G), RS1001702239 (9:35823123 C>T), RS1002138757 (9:35823339 A>G), RS1002145115 (9:35828052 G>C), RS1002629484 (9:35825091 C>G), RS1002853094 (9:35822326 CCT>C), RS1003029377 (9:35829595 C>A,T), RS1003686426 (9:35817137 T>C), RS1003712765 (9:35820068 C>A,G), RS1003747524 (9:35816799 G>A,C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009597_180	Multiple sclerosis	8.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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