Amino acids, substitutions and variant impact

This site provides insights into the nature of the amino acids and how they substitute for each other. It is an update on a series of pages first developed in 1999 to aid geneticists who used to ask Rob a lot of questions about amino acids and what did it mean to change from one to another. Since then, the pages have remained the most accessed tools we've ever developed and the Book Chapter describing them has been cited more than 1000 times. We thought it was high time to update them. If you love the 1990s style old pages, you can still see them at aasold.russelllab.org.

Venn diagram of the amino acids and common modifications

There are pages with information on each amino acid, in addition to others talking more generally about concepts. You can access these easily by using this clickable Venn diagram:

AA Venn diagram Hydrophillc Negative Charged Positive Hydrophobic C-beta branched Aromatic Aliphatic Tiny Small The main-chain Asparagine (Asn,N) Glutamine (Gln,Q) Aspartate (Asp,D) Glutamate (Glu,E) Phosphoserine (pSer,pS) Phosphothreonine (pThr,pT) Phosphotyrosine (pTyr,pY) Phosphohistidine (pHis,pH) Sulfotyrosine (sTyr,sY) Histidine (His,H) Phenylalanine (Phe,F) Tryptophan (Trp,W) Tyrosine (Tyr,Y) Arginine (Arg,R) Methylarginine (meArg,meR) Dimethylarginine (idmeArg,dimeR) Dimethylarginine (idmeArg,dimeR) Lysine (Lys,K) Methyllysine (meLys,meK) Dimethyllysine (dimeLys,dimeK) Trimethyllysine (trimeLys,trimeK) Threonine (Thr,T) Serine (Ser,S) Glycine (Gly,G) Cystine (Cys,C) Alanine (Ala,A) Proline (Pro,P) Valine (Val,V) Isoleucine (Ile,I) Methionine (Met,M) Leucine (Leu,L) Acetyllysine (acLys,acK)

Standard 20 amino acids

In case the above fails, here are links to the amino acids and groups, in addition to some other pages.

Ala Cys Asp Glu Phe Gly His Ile Lys Leu
Met Asn Pro Gln Arg Ser Thr Val Trp Tyr

Common post-translational modifications

pSer pThr pTyr pHis sTyr acLys meLys dimeLys triemeLys meArg dimeArg trimeArg

Property groups

Hydrophobic Aliphatic Aromatic Polar/Hydrophilic Charged Small Tiny C-beta branched The main chain

Other pages

Functional site tendencies
Evolutionary conservation
Substitution matrices
Some of our studies of genetic variants

Average consequences of specific amino acid changes

New for the AA site, here are some guides to what happens when you change one amino acid to another. Upper case pairs are those accessible by a single codon change.
A C D E F G H I K L M N P Q R S T V W Y
A - ac AD AE af AG ah ai ak al am an AP aq ar AS AT AV aw ay
C ca - cd ce CF CG ch ci ck cl cm cn cp cq CR CS ct cv CW CY
D DA dc - DE df DG DH di dk dl dm DN dp dq dr ds dt DV dw DY
E EA ec ED - ef EG eh ei EK el em en ep EQ er es et EV ew ey
F fa FC fd fe - fg fh FI fk FL fm fn fp fq fr FS ft FV fw FY
G GA GC GD GE gf - gh gi gk gl gm gn gp gq GR GS gt GV GW gy
H ha hc HD he hf hg - hi hk HL hm HN HP HQ HR hs ht hv hw HY
I ia ic id ie IF ig ih - IK IL IM IN ip iq IR IS IT IV iw iy
K ka kc kd KE kf kg kh KI - kl KM KN kp KQ KR ks KT kv kw ky
L la lc ld le LF lg LH LI lk - LM ln LP LQ LR LS lt LV LW ly
M ma mc md me mf mg mh MI MK ML - mn mp mq MR ms MT MV mw my
N na nc ND ne nf ng NH NI NK nl nm - np nq nr NS NT nv nw NY
P PA pc pd pe pf pg PH pi pk PL pm pn - PQ PR PS PT pv pw py
Q qa qc qd QE qf qg QH qi QK QL qm qn QP - QR qs qt qv qw qy
R ra RC rd re rf RG RH RI RK RL RM rn RP RQ - RS RT rv RW ry
S SA SC sd se SF SG sh SI sk SL sm SN SP sq SR - ST sv SW SY
T TA tc td te tf tg th TI TK tl TM TN TP tq TR TS - tv tw ty
V VA vc VD VE VF VG vh VI vk VL VM vn vp vq vr vs vt - vw vy
W wa WC wd we wf WG wh wi wk WL wm wn wp wq WR WS wt wv - wy
Y ya YC YD ye YF yg YH yi yk yl ym YN yp yq yr YS yt yv yw -

Analysis of specific variants or proteins/genes

Also new, you can now see individual (i.e. specific protein/position/change) variants and the data we have precomputed based on Schmenger et al, npj Genomic Med, 2022 (PubMed). These are accessible by using this URL format: aas.russelllab.org/variant/uniprot-accesssion/modificiation, for instance:

aas.russelllab.org/variant/TP53/M160V (Missense)
aas.russelllab.org/variant/BRAF/V600E (Missense)
aas.russelllab.org/variant/ALK/G223_M971del (Deletion)
aas.russelllab.org/variant/NBAS/E943* (Stop-gain)
aas.russelllab.org/variant/CD79B/A206fs (Frameshift)
aas.russelllab.org/variant/IRF8/S416fs (Frameshift)
aas.russelllab.org/gene/FGFR1 (Show known variants, etc. in a single gene)

There are also thousands of these links in the pages above (i.e. about amino acid changes).

You can also provide a list of variants using this page.

Citation: M.J. Betts, R.B. Russell. Amino acid properties and consequences of subsitutions. In Bioinformatics for Geneticists, M.R. Barnes, I.C. Gray eds, Wiley, 2003.
Author: Rob Russell, Heidelberg University